Cationic and ionizable lipids

A1I4R2C18-2 is a cationic / ionizable lipid disclosed in WO2023142167A1 for nucleic-acid delivery research. Its structure contains two linoleoyl chains and dimethylaminopropyl substituents on a bis-amide scaffold. In the patent’s intravenous luciferase-mRNA screen in C57BL/6 mice, the A1I4R2C18-2 formulation gave a splenic luminescence reading of 3.18 × 10³ at the 6-hour endpoint. The study used a four-component formulation containing the test lipid, cholesterol, DSPC and DMG-PEG. This result supports investigation of spleen-associated mRNA expression; organ selectivity and product-specific safety were not established by this table.

A1I4R13C18-2 is a cationic / ionizable lipid disclosed in WO2023142167A1 for nucleic-acid delivery research. Its structure contains two linoleoyl chains and azepan-1-ylethyl substituents on a bis-amide scaffold. In the patent’s intravenous luciferase-mRNA screen in C57BL/6 mice, the A1I4R13C18-2 formulation gave a splenic luminescence reading of 2.85 × 10⁴ at the 6-hour endpoint. The study used a four-component formulation containing the test lipid, cholesterol, DSPC and DMG-PEG. This result supports investigation of spleen-associated mRNA expression; organ selectivity and product-specific safety were not established by this table.

FS01 is a squaramide-containing ionizable lipid investigated for local mRNA delivery to joints. In a head-to-head mouse intra-articular screen, FS01 lipid nanoparticles produced higher luciferase expression than formulations containing Lipid 5, SM-102 or LP01 under the tested conditions. FS01 was subsequently used to deliver IL-1Ra mRNA and a C-terminal truncated ANGPTL3 mRNA (ANL3), individually or in combination. The combined formulation was evaluated in mouse rheumatoid arthritis and osteoarthritis models for suppression of inflammation and preservation of cartilage. These findings support research into intra-articular mRNA delivery; the therapeutic results concern the complete mRNA-loaded formulation.

Lipid-392 is a hydrazide-linked ionizable lipid with three tertiary amines, three palmitoyl-containing branches and a hydroxyl-bearing C10 arm. It is the carrier lipid in an optimized, cholesterol-free simplified targeted lipid nanoparticle (stLNP) containing Lipid-392, POPE and DMG-PEG2000 at 90:8.5:1.5 mol%. In mice, this formulation produced 4.93-fold greater lung luciferase expression than DOTAP-5-LNP at 0.25 mg/kg intravenous mRNA dosing, with approximately 99% of the measured lung/liver/spleen expression signal in the lung. The study also demonstrated lung-cell Cre reporter activation, adenine base editing, siRNA-mediated gene silencing and IL-10 mRNA delivery in an acute lung injury model. These preclinical results support evaluation for pulmonary RNA delivery; activity depends on formulation, payload and experimental conditions.

CQ-12 (CQ12) is a chloroquine-derived, autophagy-inhibitory lipidoid containing a 7-chloroquinoline headgroup and a hydroxyl-bearing C12 lipid chain. It was selected from the CQ6–CQ18 series for incorporation into autolysosomal degradation-inhibitory lipid nanoparticles (AUDI-LNPs). Replacing 30% of the SM-102 molar fraction with CQ-12 produced a five-component formulation containing 15 mol% CQ-12 and increased luciferase expression approximately 5.3-fold in HEK293T cells under the reported conditions. The study also evaluated CQ-12-substituted MC3 and ALC-0315 formulations, subcutaneous and intravenous mRNA delivery, and local intratracheal delivery. IL-10 and TGF-β mRNA formulations were investigated in mouse models of psoriasis and acute lung injury, respectively. CQ-12 supports research into autophagy-modulating LNPs and cytokine mRNA delivery.

A18B8C14 is an α-branched amine ionizable lipid developed using the photochemistry-based ionizable lipid library (PILL) platform. Its structure contains two secondary amines linked by a pentamethylene spacer and two ester-containing branched hydrophobic arms. A18B8C14 was identified as a lead for mRNA delivery; the publication reports higher in vivo expression with its optimized LNP formulation than with an MC3-based benchmark. The supporting information documents intravenous reporter-mRNA delivery, formulation screening, cellular uptake and endosomal colocalization, particle stability, and dose-dependent blood chemistry. It is intended for research on mRNA-LNP formulation and delivery.

DA lipid is a dopamine-derived ionizable lipid incorporating a catechol antioxidant headgroup, one tertiary amine and two ester-linked branched hydrophobic tails. In the cited study, DA lipid and DA lipid nanoparticles scavenged reactive oxygen species more effectively than their oxidized ODA counterparts. DA LNPs supported higher mRNA-derived protein expression than ODA LNPs in DC2.4 cells and after intramuscular administration in mice, with expression comparable to ALC-0315 LNPs. OVA mRNA-loaded DA LNPs improved antigen presentation and suppressed tumor growth in a prophylactic B16-OVA melanoma model relative to ODA LNPs. These results support research into antioxidant mRNA delivery and preventive cancer vaccination.

U-502 is a Janus dendritic ionizable lipid with two tertiary amines, two hydroxyl groups and six C8 alkyl tails attached through ether-containing dendrons and ester linkers. In a 16-lipid study, U-502 and U-503 were the leading intravenous mRNA-expression candidates, with modestly higher luciferase signals than ALC-0315 in BALB/c mice at 0.5 mg/kg mRNA and a 3-hour readout. The U-502 formulation had a reported size of 108 nm, PDI of 0.125, apparent LNP pKa of 6.36 and mRNA encapsulation efficiency of 91.83%. U-502 also underwent cell transfection, lysosomal colocalization and representative tissue-histology studies. It supports preclinical research into liver-dominant systemic mRNA delivery and headgroup–tail structure–activity relationships.

U-503 is a Janus dendritic ionizable lipid with two tertiary amines, two hydroxyl groups, two ester linkers and six C10 alkyl tails connected to dendritic cores through ether bonds. It was identified alongside the C8-tail analogue U-502 as a leading intravenous mRNA-expression candidate in a 16-lipid study. In BALB/c mice given 0.5 mg/kg luciferase mRNA, U-503 produced a modestly higher 3-hour expression signal than the ALC-0315 comparator under the reported formulation conditions. Its LNP formulation had a size of 114 nm, PDI of 0.122, apparent LNP pKa of 6.31 and encapsulation efficiency of 89.36%. U-503 is a preclinical research candidate for systemic mRNA delivery and matched tail-length comparisons with U-502.

U-510 is a three-tail Janus dendritic ionizable lipid containing an N-methyl tertiary amine, a hydroxypropyl head segment, an ester linker and three C8 ether-linked hydrophobic tails. In an intravenous luciferase-mRNA study in BALB/c mice, it showed a spleen-biased organ-expression profile within the U-509–U-512 series. The authors reported 52% spleen-targeting efficiency in the context of liver and spleen luminescence at 3 hours after 0.5 mg/kg mRNA; this is not a percentage of transfected spleen cells or injected dose. The U-510 LNP formulation had a reported size of 113 nm, PDI of 0.146, apparent LNP pKa of 6.38 and encapsulation efficiency of 87.88%. It supports preclinical evaluation of splenic mRNA expression rather than maximum whole-animal expression.

iL-19 is an aminoethoxy-functionalized ionizable lipid with a triamine scaffold, two ester linkages and four doubly branched hydrophobic tails. It was identified as the overall lead for circular RNA delivery in a 2026 JACS study. With circRNA encoding firefly luciferase, iL-19 LNPs produced approximately 28-fold higher expression than the SM-102 benchmark in C2C12 cells and approximately 2.5-fold higher expression after intramuscular administration in BALB/c mice under the reported conditions. The reported circRNA formulation uses iL-19, DSPC, cholesterol and DMG-PEG2000 at 50:10:38.5:1.5 mol%. It supports preclinical investigation of circular RNA delivery to muscle; comprehensive safety and immunogenicity evaluation remains outstanding.

PA97MD101 is an ester-containing ionizable lipid with a tetraethylenepentamine-derived headgroup and two branched hydrophobic ester arms. Identified through machine-learning-guided screening and independent animal validation, its LNPs produced approximately fourfold higher hepatic luciferase expression than SM-102 in mice after intravenous Fluc mRNA delivery at 0.1 mg/kg. The study also demonstrated Cre-dependent liver recombination and Cas9/sgTtr-mediated TTR suppression. Formulation-dependent activity was associated with acidic-pH membrane activity and reduced lysosomal colocalization. PA97MD101 is a preclinical research candidate for hepatic mRNA and CRISPR cargo delivery.

MP2 is a methylprednisolone-derived ionizable lipid studied for local colonic mRNA delivery. Its IL-35 mRNA LNP formulation was evaluated in acute and chronic colitis mouse models and ex vivo human colonic biopsies.

Lipid 03-135 is an ionizable lipid investigated for lipid nanoparticle delivery of mRNA encoding a CD19/CD3 bispecific T-cell engager developed by Abogen. In WO2024131874A1, its formulation showed the highest plotted serum antibody concentrations at 24 and 48 hours among five tested lipids after a single intravenous dose of mRNA1 in NOD/SCID mice.

Ionizable lipid used for intravenous mRNA-encoded CD19/CD3 bispecific antibody delivery and an antitumor study in a human PBMC / Nalm6 leukemia model.

BP-200-C12 is a bisphosphonate-linked ionizable lipid selected from a 21-member library in Liu et al. for local RNA delivery at mineralized tissue interfaces.

Lipid 6 is a literature-reported ionizable lipid for ex vivo mRNA delivery to primary human T cells. In Gao et al. (2026), LNPs containing Lipid 6 generated MUC1-CAR T cells that were assessed against MUC1-positive cancer cell lines in vitro.

LC-1 (LC-lipid-1) is an ionizable lipid identified by screening a 384-member Ugi-reaction library with a large, 5.7-kb ABE–NanoLuc mRNA cargo. The cited study evaluated LC-1 lipid nanoparticles for delivery of Cas9 and base-editing cargos to the liver, brain and lung in mice, using different formulations and administration routes.

HI-62 is a cyclic-thiourea ionizable lipid reported as a lead component of onion-like multilamellar mRNA-LNPs. In the cited preprint, its E21 formulation supported high mRNA encapsulation, sustained reporter expression, frozen-storage stability and antitumor activity in a preclinical mRNA-vaccine model.

Lipid SG5 is a dual-amine ionizable lipid developed for systemic, lung-selective mRNA delivery. Its two tertiary amines and two C16 β-hydroxy tails support stepwise protonation in the reported fSG5 LNP system. The cited preclinical study evaluated pulmonary luciferase expression, functional Cre mRNA delivery and Nrf2 mRNA delivery in an acute lung-injury model.

Lipid 43 is an ionizable lipid disclosed as Compound 43 in WO 2024/109794. In the patent's TMF30 formulation, mRNA-LNPs showed predominantly splenic reporter expression after administration in mice. Its structure, molecular formula, molecular weight and SMILES were assigned from the compound-specific synthesis scheme and checked against the reported proton count.

The LUMI-6 lipid, autonomously designed via the LUMI-lab platform, is a brominated ionizable lipid optimized for mRNA delivery. Formulated at a molar ratio of 35:28:34.5:2 (LUMI-6:DOTAP:cholesterol:C14-PEG2000), LNPs exhibit uniform physicochemical properties, including a hydrodynamic diameter of ~80 nm, polydispersity index (PDI) <0.2, and robust mRNA encapsulation efficiency. In vitro, LUMI-6 LNPs demonstrated 1.8-fold higher transfection potency in human bronchial epithelial cells compared to its debrominated counterpart (LUMI-6D), with minimal cytotoxicity confirmed by CCK-8 assays. In vivo, pulmonary delivery of CRISPR-Cas9 mRNA via LUMI-6 LNPs achieved ​20.3% gene editing efficiency in murine lung epithelial cells, surpassing SM-102 (Moderna’s clinical benchmark) and demonstrating ​preferential tropism for lung epithelium over endothelial cells—critical for inhaled therapies targeting cystic fibrosis and surfactant disorders. The brominated tail enhances endosomal escape through optimized protonation dynamics, though explicit pKa values remain unmeasured. Synthesized via high-throughput combinatorial chemistry and refined through AI-driven active learning, LUMI-6 combines scalable production with organ-selective delivery, positioning it as a transformative platform for pulmonary nucleic acid therapeutics.

503O8,12 is a branched-tail ionizable lipidoid prepared from amine head 503 and saturated 2-octyldodecyl acrylate. In a four-component, DOPE-containing LNP, it produced predominantly splenic reporter expression after intravenous mRNA administration in mice. It is a research candidate for extrahepatic mRNA formulation screening; cell-specific spleen delivery and therapeutic efficacy were not established in this study.

6Ac1-C12 is an ionizable cationic lipid with a hexaester degradable core and six C12 hydrophobic alkyl tails, featuring a pKa around 6.0 and strong endosomal escape capacity. Its four-component LNPs deliver mRNA mainly to liver endothelial cells after IV injection and remain stable for 30 days at 4°C. Formulated without cholesterol, its three-component system enables lung-targeted delivery with low in vivo toxicity, and the ester core facilitates biodegradation for versatile mRNA applications.

​TOT-5​​, a tri-oleoyl-Tris ionizable lipid (pKa 6.2), enables splenic B cell-targeted mRNA delivery via 15% DSPC-incorporated LNPs. Its charge-neutral, hydrophobic surface minimizes hepatic ApoE uptake and enhances complement C3 adsorption, facilitating CD21/35-mediated uptake by marginal zone B cells. In vivo, intravenous 15%DSPC-LNPs showed 8-fold higher spleen-to-liver luciferase expression vs 3%DSPC, with anti-CD21/35 blocking 60% B cell uptake. Intramuscular administration induced robust OVA-specific IgG (10^5 titer) and CTL responses (3.5% tetramer+ CD8+ T cells) while reducing hepatotoxicity (ALT/AST levels ≤40 U/L vs SM-102-LNPs' 80-120 U/L). Cryo-ET confirmed stable lamellar structures (80-100 nm, ζ-potential -2 mV). This formulation achieves safe, ligand-free splenic targeting for mRNA vaccines.

11-10-8 is a degradable, branched ionizable lipidoid identified in a combinatorial screen for mRNA delivery. In the cited mouse study, its optimized LNP formulation supported liver-directed reporter mRNA expression, TTR gene editing with Cas9 mRNA and sgRNA, and FGF21 mRNA expression in a diet-induced obesity model.

CL15F 7-5 is a piperidine-based ionizable lipid from the CL15F library, characterized by a symmetrically branched tail structure with a 7-carbon main chain and a 5-carbon side chain. This moderate tail length positions it between short-tail (e.g., CL15F 6-4) and long-tail (e.g., CL15F 14-12) variants, granting it a unique balance in mRNA delivery properties. Its LNPs exhibit optimized organ selectivity, enabling significant mRNA expression in both the spleen and muscle, as demonstrated by in vivo luciferase assays following intravenous and intramuscular administration. This lipid structure facilitates a favorable DSPC surface density on LNPs, which moderates interactions with serum proteins like ApoE, thereby reducing rapid hepatic clearance and promoting extrahepatic delivery. In vaccine applications, CL15F 7-5 LNPs encapsulating SARS-CoV-2 RBD mRNA elicited robust anti-RBD IgG titers and neutralizing antibodies in mice, outperforming the clinically benchmarked SM-102 lipid. The piperidine headgroup further contributes to storage stability by minimizing the generation of aldehyde impurities that can form mRNA-lipid adducts. Consequently, CL15F 7-5 represents a versatile lipid for developing stable, spleen-targeted mRNA vaccines and therapeutics, leveraging tail-length engineering for enhanced efficacy without complex formulation changes.

CICL 207 is structurally optimized based on Lipid CICL-1. CICL207​​ is a constrained ionizable cationic lipid designed for lipid nanoparticle (LNP) delivery systems developed by Capstan. Its structure features a ​​rigid cyclic backbone​​ (e.g., pyrrolidine-derived core) paired with a ​​tertiary amine group​​ that ionizes at acidic pH (pKa ~6.5–7.0), enhancing endosomal escape. The lipid includes ​​asymmetric hydrophobic tails​​ (likely C14–C18 alkyl/ester chains) to stabilize LNP membranes and improve nucleic acid encapsulation. Integrated into LNPs (e.g., 58% CICL-207, 10% DSPC, 30.5% cholesterol, PEG-lipids), it enables targeted delivery to T cells (anti-CD5/CD8 tLNPs) with ​​high transfection efficiency​​ (spleen T cells >70% mCherry+), ​​reduced liver uptake​​, and ​​low toxicity​​ (no significant ALT/AST elevation in rats). Its constrained design balances stability, tissue specificity, and biocompatibility for gene therapy applications.CICL 207 (F50) significantly outperforms CICL-1 by delivering dramatically enhanced target cell transfection with reduced off-target effects. It achieves >50% transfection efficiency in splenic T-cells—nearly double that of CICL-1—while slashing off-target expression in liver cells to <5% (versus >15% for CICL-1. This precision translates to superior therapeutic outcomes: CICL-207 enables ~95% B-cell depletion in CAR-T applications, far exceeding CICL-1 ’s ~60% efficacy. Critically, it maintains an exceptional safety profile, showing no significant liver toxicity or inflammatory cytokine elevation even at high doses. Furthermore, CICL-207 demonstrates 2-fold higher transfection efficiency in hematopoietic stem cells, enabling robust gene editing. Its optimized pKa (~6.5) and constrained amine structure enhance endosomal escape while minimizing Kupffer cell uptake, making it ideal for targeted therapeutics requiring both potency and safety.​

ALC 0307 is an ionizable amino lipid developed by Acuitas Therapeutics, serving as the critical functional component in lipid nanoparticles (LNPs) for targeted therapeutic delivery. As the core cationic lipid in specific LNP formulations (e.g., k-abe for CPS1-Q335X correction), its key feature is pH-dependent chargeability: it remains neutral at physiological pH but becomes positively charged in acidic environments like endosomes. This property enables efficient encapsulation of nucleic acid payloads (>97% efficiency, e.g., base editor mRNA/gRNA complexes) and facilitates endosomal escape via membrane disruption post-cellular uptake.​​ Its optimized structure promotes selective hepatocyte targeting by binding endogenous apolipoprotein E (ApoE), which subsequently interacts with LDL receptors on liver cells. Preclinical studies show rapid clearance (>99.5% plasma reduction in 14 days) and manageable transient toxicity (mild, reversible cytoplasmic vacuolation in hepatocytes, short-term ALT/AST elevation). LNPs containing ALC0307, alongside helper lipids (cholesterol, DSPC, and PEG-lipid ALC-0159), form stable ~73 nm particles with low polydispersity. This combination enables repeatable, liver-directed delivery of gene editing therapeutics with minimized off-target effects, underpinning its use in individualized in vivo gene correction therapies.

PL-40​​ is a ​​cardiolipin-mimetic ionizable lipid​​ engineered for high-efficiency, antibody-free mRNA delivery to T cells. PL 40 LNPs exhibit a mean particle size of ​​120 nm​​, zeta potential of ​​-5.19 mV​​, and >80% mRNA encapsulation efficiency, with excellent plasma stability (≤5% size change after 6h in serum). Cryo-TEM reveals ​​polyhedral nanoparticles​​ with phase-separated domains, while SAXS confirms tight mRNA packing (d-spacing: ​​~3 nm​​ vs. 6.64 nm in conventional LNPs). AFM demonstrates exceptional rigidity (high bending modulus), enabling T cell-selective uptake via actin-mediated endocytosis (>2× higher than ALC0315 LNPs).In primary human T cells, PL40 LNPs achieve ​​>90% transfection​​ at 0.5 μg mRNA dose and sustain >100× higher luciferase expression than benchmark lipids. When delivering circular RNA, they extend protein expression ​​>5 days​​ with superior spleen tropism (spleen:liver ratio = ​​2.63​​). Crucially, they reprogram T cells into functional CAR-Ts in vivo without antibody conjugation, evading exhaustion markers (no Tim-3/PD-1 upregulation). Therapeutically, PL40-based uPAR-targeted CAR mRNA reduces liver fibrosis (​​collagen↓50%​​, ALT↓50%) and rheumatoid arthritis severity (​​clinical scores↓60%​​) by clearing senescent cells. Humanized anti-uPAR CARs delivered via PL40 show near-complete cytotoxicity (>95%) against uPAR+ cells, underscoring clinical translatability.

AMG-1541 is a degradable cyclic amino alcohol ionizable lipid optimized for mRNA vaccine delivery using lipid nanoparticles (LNPs). Formulated typically with DOPE, cholesterol, and PEG-lipids, AMG 1541 LNPs have a diameter of ~85 nm, PDI of 0.107, and encapsulation efficiency of 67%, ensuring stability and efficient mRNA delivery. In vitro, it outperforms benchmarks like SM-102, showing enhanced transfection in cells such as C2C12 and PBMCs. In vivo, intramuscular administration in mice results in robust protein expression within 6 hours and induces potent immune responses, including high antibody titers and Th1-biased T-cell activation, with minimal inflammation. Mechanistically, its β-hydroxyl groups form hydrogen bonds with mRNA phosphate backbones, facilitating endosomal escape. AMG1541 degrades rapidly under enzymatic conditions, reducing long-term toxicity, and is effective for vaccines targeting pathogens like influenza and SARS-CoV-2, making it a promising candidate for clinical applications.

Lipid S4 is an advanced ionizable lipid engineered for systemic mRNA delivery to the brain, leveraging SR-57227—a high-affinity 5-HT3 receptor ligand—as its core head group to enable targeted blood-brain barrier (BBB) penetration via receptor-mediated transcytosis, while incorporating amino linkers for pH-responsive ionization and biodegradable branched ester tails to facilitate efficient endosomal escape and intracellular mRNA release; optimized through orthogonal screening into OS4 LNP (formulated at S4/DOPE/Chol/DMG-PEG2k = 40:40:60:0.75 molar ratio), it demonstrated a 13.3-fold increase in brain mRNA expression compared to FDA-approved MC3 LNPs, and further conjugation with the Tat cell-penetrating peptide yielded OS4T LNP, boosting delivery efficiency by 12.7-fold over OS4 alone and enabling broad mRNA expression across neurons, astrocytes, microglia, and endothelial cells; validated in orthotopic glioblastoma models, OS4T delivered engineered IL-12 mRNA, suppressing tumor growth and extending median survival to 37 days (vs. 17 days for controls) with minimal systemic toxicity, positioning S4-based LNPs as a robust, translatable platform for CNS-targeted therapeutics.

Lipid 87 is a proprietary ionizable lipid developed by Generation Bio. Used as a key ingredient in stealth LNPs, it greatly prolongs blood circulation time, maintains high nucleic acid encapsulation efficiency and low cytotoxicity, and enables effective liver targeting. Its relevant applications are documented in PCT patent WO2026/080826A1. As a core component (47.5–57.5 mol%) of stealth lipid nanoparticles (LNPs), it works synergistically with steric-stabilizing polymers like DSG-PEG₂₀₀₀-OMe to extend the in vivo blood half-life of LNPs to over 24 hours (compared to merely 30 minutes of conventional LNPs). It achieves an encapsulation efficiency above 95% for mRNA and closed-ended DNA (ceDNA), exhibits low cytotoxicity with an IC₅ value greater than 100 μM, and delivers robust liver-targeting performance, obtaining over 80% hepatocyte transfection at a dosage of 0.5 mpk. In preclinical models of hemophilia B, LNPs formulated with Lipid 87 can restore around 40% of clotting factor IX (FIX) activity for more than seven days.

Lipid 15 is the lead ionizable cationic lipid (ICL) for CD8-targeted mRNA-LNPs. As the core LNP component, Lipid 15 yields ~100 nm uniform particles with near-neutral surface charge at physiological pH, while becoming strongly cationic in acidic endosomes—reducing hepatic off-target uptake and enabling efficient endosomal escape to release mRNA. Versus other ICL candidates, Lipid 15 achieves far higher mRNA transfection efficiency in primary human CD8⁺ T cells, supports robust transient CAR expression, and triggers minimal cytokine release in immunogenicity assays. It retains structural and functional stability after freeze storage. When formulated into anti-CD8 VHH-conjugated LNPs carrying CD22 CAR mRNA, Lipid 15 drives specific in vivo reprogramming of circulating CD8⁺ T cells into functional CAR-T cells, delivering potent tumor suppression in humanized hematological malignancy models without overt toxicity.

E12LA6B603（ILB3132，ILB-3132） is a novel ionizable amino lipid disclosed in patent WO2024198497A1, developed by MagicRNA, representing a highly efficient component for lipid nanoparticle (LNP) delivery systems.When formulated into LNPs, E12LA6B603 LNP achieves a remarkable 98.26% encapsulation efficiency for mRNA. It mediates superior in vitro transfection in dendritic cells (1.8E+05 intensity) and demonstrates best-in-class in vivo protein expression after intramuscular injection (2.2E+09 intensity). Most notably, in a B16-OVA melanoma model, therapeutic OVA-mRNA vaccines delivered by E12LA6B603 LNPs induced 100% complete tumor regression, highlighting its superior efficacy over benchmarks like DLin-MC3 and SM-102. Its biodegradable ester linkages and balanced structure make it a promising, potent candidate for next-generation mRNA vaccines and therapeutics.

PyCB lipid (MeDZ) is a rationally designed zwitterionic ionizable lipid that serves as a core functional component in the novel three-component (ThrCo) lipid nanoparticle (LNP) platform. It is synthesized by covalently attaching a zwitterionic PyCB structure to the hydroxyl group of the clinically available ionizable lipid ALC-0315.Its key feature is its pH-responsive behavior. At physiological pH (~7.4), the PyCB headgroup exhibits zwitterionic properties, forming charge-assisted hydrogen bonds with water molecules (PyCB-H₂O complexes). This confers high hydrophilicity to the LNP surface, enhancing stability in aqueous environments and reducing nonspecific protein adsorption in the bloodstream. This zwitterionic surface effectively mimics and replaces PEGylated lipids, thereby avoiding PEG immunogenicity and the associated Accelerated Blood Clearance (ABC) effect upon repeated administrations.Crucially, in the acidic environment of endosomes (pH ~6.5), the PyCB group undergoes strong protonation, rapidly transforming into a cationic state (PyCB-H₃O⁺ complexes). This promotes efficient fusion with and disruption of the endosomal membrane, facilitating the escape and cytoplasmic release of encapsulated mRNA.By replacing both cholesterol and PEGylated lipids in traditional LNPs, PyCB lipid enables the redirection of LNP biodistribution from the liver to the spleen, achieving superior spleen-specific mRNA translation and enhancing antigen presentation for potent immune activation.

AMG514 is a novel ionizable lipid designed for formulating spleen-targeting lipid nanoparticles (LNPs) to deliver immune‑remodeling mRNAs (IR‑mRNAs). Its key advantage lies in the formation of a unique “protein corona” enriched with vitronectin, coagulation factors, and specific apolipoproteins (e.g., ApoA‑IV), together with its relatively high apparent pKa (~7.5), which actively redirects LNPs to the spleen instead of the liver. This precise spleen‑targeting property enables efficient transfection of splenic antigen‑presenting cells (APCs). As a vaccine adjuvant, AMG514‑LNPs therefore elicit a more robust activation of adaptive immunity compared to conventional LNPs (e.g., cKK‑E12), generating significantly enhanced antigen‑specific CD8⁺ T‑cell and antibody responses, and inducing durable anti‑tumor immune memory in preclinical models.

C12-4 (Lipid A-4,Lipid F3) is a branched-chain ionizable cationic lipidoid that has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA. LNPs containing lipid A4 and encapsulating an mRNA reporter accumulate in the uterus, placenta, and ovaries, as well as to the spleen and liver, in pregnant mouse dams unlike LNPs containing the branched-chain ionizable cationic lipidoid C12-200, which primarily accumulate in the liver. Intravenous administration of LNPs containing lipid A4 and encapsulating mRNA encoding VEGF increase placental VEGFR1 levels and mean fetal blood vessel area without inducing liver damage in pregnant mouse dams.

CICL1 (L829)​​ is a ​​novel ionizable cationic lipid​​ specifically engineered for ​​targeted lipid nanoparticles (tLNPs)​​ that enables efficient in vivo delivery of mRNA payloads to ​​CD8+ T cells​​. Designed to overcome limitations of conventional LNPs, CICL-1 (L-829)​​significantly ​​reduces off-target delivery to the liver​​ and exhibits ​​rapid clearance​​ compared to benchmark lipids like ALC-0315, while demonstrating ​​enhanced biodegradability and tolerability​​ in rodent and primate models. When incorporated into CD8-targeted tLNPs, CICL 1 (L829 enables ​​preferential transfection of CD8+ T cells​​ over other immune subsets, facilitating the generation of functional ​​anti-CD19 or anti-CD20 CAR T cells directly *in vivo​​*. These tLNP-engineered CAR T cells mediate ​​rapid, deep B-cell depletion​​ in humanized mice and cynomolgus monkeys, with repopulating B cells exhibiting a naïve phenotype suggestive of immune reset. By eliminating the need for ex vivo manufacturing or lymphodepleting chemotherapy, the L829-tLNP platform represents a ​​safer, scalable approach​​ for accessible CAR T therapy in oncology and autoimmune diseases.

D-Lin-MC3-DMA(MC3) is the most potent cationic lipid that has been synthesized for Lipid nanoparticles (LNPs) to deliver the siRNA.

DLin-DMA is an ionizable amino lipid with cationic properties and a pKa of 6.7. It is widely utilized in lipid nanoparticle (LNP) formulations alongside helper lipids to enable efficient nucleic acid delivery.

DLin-KC2-DMA is a highly potent ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of siRNA. It represents a significant advancement over earlier generations of lipids, such as DLin-DMA, due to its dramatically improved gene silencing efficiency.

LP-01 is an ionizable cationic amino lipid (pKa = ~6.1). It has been used in the generation of lipid nanoparticles (LNPs). LNPs containing LP-01 and encapsulating both Cas9 mRNA and modified single-guide RNA (sgRNA) for the transport protein transthyretin (Ttr) induce gene editing in liver cells in mice in a dose-dependent manner resulting in reduced serum Ttr levels for at least 12 months.

SM86 is a cationic, ionizable lipid developed by Moderna as a core component of its lipid nanoparticle (LNP) platform for mRNA therapeutic delivery.SM-086 is structurally optimized and analogous to SM-102 (used in Moderna’s COVID-19 vaccines), with modifications aimed at enhancing mRNA delivery efficiency and safety.SM-86 serves as the primary cationic lipid in three investigational mRNA therapies targeting rare metabolic disorders:mRNA-3927: Restores propionyl-CoA carboxylase activity in propionic acidemia (PA). mRNA-3705: Delivers methylmalonyl-CoA mutase mRNA for methylmalonic acidemia (MMA). mRNA-3210: Provides phenylalanine hydroxylase mRNA to treat phenylketonuria (PKU).

DODMA, also known as MBN 305A is a a cationic lipid containing the unsaturated long-chain (18:1) oleic acid inserted at both the sn-1 and sn-2 positions. It has been used in the composition of lipospomes formulated as stable nucleic acid lipid particles that can encapsulate siRNA or other small molecules to be used for drug delivery

DODAP, also known as 1,2-Dioleoyl-3-dimethylammonium-propane, is a cationic lipid. It has been used as a component in liposomes that can be used to encapsulate siRNA, immunostimulatory oligodeoxynucleotides, antisense oligonucleotides, or chemotherapeutic agents for in vitro and in vivo delivery.

DOTAP, also known as 1,2-Dioleoyl-3-trimethylammoniumpropane, is a cationic liposome-forming compound used for transfection of DNA, RNA, and other negatively charged molecules into eukaryotic cells. It has been used in gene delivery vectors for gene ther

NT1-O12B is a tryptamine-derived bioreducible lipidoid evaluated as a brain-delivery component. The cited study identified NT1-O12B as the strongest DiR brain-delivery member of the tested NT-lipidoid series and used it with PBA-Q76-O16B at a 3:7 weight ratio for optimized DiR and amphotericin B delivery. Results apply to these formulations and must not be extended to the NT1-O14B systems used for Tau-ASO and Cre protein delivery.

ALC-0315 is an ionisable aminolipid that used for mRNA compaction and aids mRNA cellular delivery. ALC-0315 can be used to form lipid nanoparticle (LNP) delivery vehicles.

DLin-KC3-DMA, a nucleic acid, shows in vivo silencing activity. DLin-K-C3-DMA can be used in the synthesis of nucleic acid-lipid particle to delivery of nucleic acid.

CKK-E12 is a ionizable lipid in combination with other lipids make up the lipid nanoparticles which are used to deliver RNA-based therapeutics. cKK-E12 was highly selective toward liver parenchymal cell in vivo.Multitail lipids usually have three or more tails and tend to form more cone-shaped structures due to the increase of tail crosssection, which enhances the endosome escape and mRNA delivery efficiency.CKK-E12 is an ionizable lipid with four lipid tails and diketopiperazine core-based head. It has shown excellent efficiency in delivering CRISPR-Cas9 mRNA and sgRNA.cKK-E12 iLNPs encapsulated mRNA was used to investigate the effect of Toll-like receptor 4 (TLR4) on iLNPsmediated mRNA delivery, and it has been demonstrated that the targeting, safety and efficacy of iLNPs are closely related to disease state. In other words, even though iLNP delivers therapeutic mRNA to a given cell type in one disease state, it is not guaranteed to deliver mRNA to the same cell type in another disease. As same as MC3 and C12-200, CKK-E12 is also used to be a positive control ionizable lipid when exploiting new ionizable lipids.

503O13 is a degradable, four-tail ionizable lipidoid from a second-generation siRNA-delivery library. In the cited mouse Factor VII study, the non-optimized 500-series formulation was screened at 5 mg/kg and optimization of the 503O13 formulation reduced its reported EC50 to 0.01 mg/kg. The exact optimized helper-lipid molar ratio was not disclosed. Results below apply to the cited LNP, not to the neat lipid or a commercial batch.

5A2-SC8 is a dendrimer for miRNA delivery to late-stage liver tumors with low hepatotoxicity. 5A2-SC8 shows potent EC50 < 0.02 mg/kg (siRNA against FVII (siFVII)) in dose-response experiments, and well tolerated in separate toxicity studies in chronically ill mice bearing MYC-driven tumors. 5A2-SC8 is a degradable lipid-like compound (ester-based dendrimer) for small RNAs delivery.5A2-SC8, was obtained by screening a large library of more than 1500 ester-based dendrimers containing ionizable amino groups, which have three tertiary amine heads and five lipid tails. Based on this library, the in vitro transfection efficiency of different formulations of 5A2-SC8 iLNPs was evaluated, discovering the optimal formulation (5A2-SC8, DOPE, cholesterol, PEG at a molar ratio of 15:15:30:3) of 5A2-SC8 iLNPs for delivering fumarylacetoacetate hydrolase (FAH) mRNA to liver.After the intravenous injection via tail, the model mice of hepatorenal tyrosinemia type I had strong FAH protein expression, which prevented body weight loss and increased the survival rate of hepatorenal tyrosinemia mice . In addition to introducing utility of 5A2-SC8 iLNPs for the therapeutic intervention, the 5A2-SC8 iLNPs containing DOTAP have been used to establish complex mouse models via intravenous injection, including in situ liverspecific cancer model and in situ lung-specific cancer model. Based on this iLNPs delivery system, 5A2-SC8 induced model construction method overcomes the time-consuming and costly disadvantages of traditional animal models establishing methods, including transgenesis and gene engineering in embryonic stem cells.

FTT5 is a lipid-like compound for efficient delivery of long mRNAs in vivo.

246C10 is a synthesized ionizable lipid. 246C10 can be formulated into lipid nanoparticles (LNPs) with dioleoylphosphatidylethanolamine (DOPE), cholesterol, and C16-PEG2000 ceramide (PEG-lipid) as well as mRNA. The lipid nanoparticle formulations can be used for mRNA delivery. To obtain iLNPs that could specifically target liver sinusoidal endothelial cells (LSECs), six different ionizable lipids (241C10 to 246C10) were synthesized by an epoxide ring-opening reaction with piperazine- or piperidine-containing amines. Biodistribution and gene regulation of various iLNPs were assessed in vivo, and the results showed that the 246C10 iLNPs (containing piperazine amine) had the highest luciferase expression in the liver. When further analyzing the 246C10 iLNPs transfection efficiency in different types of liver cells, it was found that tdTomato fluorescence was mainly concentrated in hepatocytes, not in LSECs. Figure 6f shows that 80% of hepatocytes are fluorescent, 40% of LSECs are fluorescent, and 20% of Kupffer cells are fluorescent. Due to the mannose receptor on LSECs, mannose-PEG lipid was introduced into 246C10 iLNPs to alter the distribution of iLNPs in different liver cells. As shown in Figure 6g, tdTomato fluorescence distribution was 15% of hepatocytes, 70% of LSECs, and 15% of Kupffer cells, significantly improved the ability of iLNPs to actively target LSECs. In contrast, this work indirectly shows that the iLNPs with piperazine head lipid are more able to deliver mRNA to the liver and translate the target protein than the iLNPs with piperidine head lipid. It is worth mentioning that the preparation buffer of 246C10 iLNPs could influence the encapsulation efficiency of mRNA. With the addition of sodium chloride in the citrate buffer, the encapsulation efficiency of CRISPR-Cas9 mRNA and sgRNA was increased. These iLNPs were able to treat hemophilia safely, without causing hepatotoxicity, the immune response induced by Cas9 and off-target editing.

SM-102 is an ionizable amino lipid that has been used in combination with other lipids in the formation of lipid nanoparticles.Administration of luciferase mRNA in SM-102-containing lipid nanoparticles induces hepatic luciferase expression in mice. Formulations containing SM-102 have been used in the development of lipid nanoparticles for delivery of mRNA-based vaccines.

93-O17S is an imidazole-based synthetic lipidoid for in vivo mRNA delivery. Lipid nanoparticles (LNPs) with 93-O17S promotes both the cross-presentation of tumor antigens and the intracellular delivery of cGAMP (STING agonist).

C24 is a novel multiprotic ionizable lipid. C24 lipid nanoparticle (LNP) has a multistage protonation behavior resulting in greater endosomal protonation and greater translation compared to the standard reference MC3 LNP. C24 LNP also lower injection site inflammation and higher stability compared to MC3 LNP.

L319 (LIPID 319) is a novel ionizable, biodegradable lipid for delivery of short interfering RNAs (siRNAs). L319-LPN displays rapid elimination with pKa of 6.38 and also shows well tolerated up to 10 mg/kg.

ATX-126(ATX-0126, 10p) is an ionizable cationic lipid (pKa = 6.38).It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA. Intravenous administration of LNPs containing ATX-126(ATX-0126, 10p) and encapsulating Factor VII siRNA decrease Factor VII blood levels in mice.

Lipid A9 is an ionizable cationic lipid (pKa = 6.27) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA and siRNA in vivo. LNPs containing lipid A9 and encapsulating non-stimulatory siRNA increase plasma levels of chemokine (C-C motif) ligand 2 (CCL2), indicating activation of the innate immune response, and decrease body weight in mice.

C12-200 is a well-known cationic lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of therapeutic nucleic acids, including siRNA, mRNA, and CRISPR components. It is widely recognized for its high in vivo potency at low doses and is often used as a positive control ionizable lipid in research exploring new ionizable lipids.

ssPalmO-Phe(SS-OP) is a self-degradable material for the delivery of oligonucleotides. ssPalmO-Phe is a self-degradable derivative of ssPalm that is self-degraded in the intraparticle space by a specific hydrolytic reaction. ssPalmO-Phe is beneficial for overcoming the plasma/endosomal membrane, LNP-ssPalmO-Phe can be used to deliver both nucleic acids.

C14-4 (C14-494,Lipid B-4,Lipid B4) is a novel ionizable lipid with the highest T-cell transfection efficiency and low cytotoxicity.The C14-4 ionizable lipid has been explored for CAR-T therapy.To screen the excellent formulations for mRNA delivery, a lipid library of 24 ionizable lipids was constructed to make iLNPs, which were used to deliver luciferase mRNA into Jurkat cells.[115] The optimal iLNPs formulation was C14-4 iLNPs (C14-4 ionizable lipid, DOPE, chol, and PEG at a molar ratio of 35%, 16%, 46.5%, and 2.5%) (Figure 6c). The optimal dose of luciferase mRNA for C14-4 iLNPs was 30 ng. Compared with electroporated CAR T cells, the CAR T cells engineered via C14-4 iLNPs showed potent cancer-killing activity when they were cocultured with Nalm-6 acute lymphoblastic leukemia cells. To obtain a safer and more effective CAR mRNA delivery vehicle, the orthogonal design provided 256 potential formulations, and 16 representative iLNPs formulations were evaluated.Through evaluating the safety, delivery efficiency, and transfection efficiency of 16 iLNPs, the formulation B10 (C14-4 ionizable lipid, DOPE, chol, PEG at a molar ratio of 40%, 30%, 25%, and 2.5%) was screened out as the optimal performing formulation. The luciferase expression based on B10 formulation was increased threefold than the initial formulation. Reducing the accumulation and clearance of iLNPs in the liver can increase the expression of CAR mRNA in T cells, further improving the therapeutic effect of CAR-T. Studies have shown that cholesterol analogs can alter the mechanisms of intracellular circulation and enhance the delivery of mRNA, which may be related to the reduced recognition of iLNPs by the Niemann Pick C1 (NPC1) enzyme.The addition of a hydroxyl group to various locations in the cholesterol molecule can alter the binding kinetics between the modified cholesterol and NPC1, and reduced NPC1 recognition of cholesterol. The results showed that replacement of 25% and 50% 7 α-hydroxycholesterol for cholesterol in iLNPs improved mRNA delivery to primary human T cells in vitro by 1.8-fold and twofold, respectively.C14-4 is one of the ionizable lipids to efficiently deliver mRNA to Jurkat cells or primary human T cells. It will effectively promote the development of mRNA delivery by iLNPs for CAR-T therapy.

Genevant CL1 (lipid 10) is a novel ionizable lipid for rna delivery.Lipid 10 rapidly accumulated in the liver within the first hour of dosing (reflecting LNP uptake), but levels then steadily declined over the ensuing 2 weeks period, similar to MC3.Lipid 10 afforded more than double the expression of either approved lipid. We also observed high splenic expression for ALC-0315, which correlated with higher MCP-1 levels.Animals received a single 5 µg IM dose of LNP encapsulating firefly luciferase (fLuc) mRNA. Whole body imaging was performed 6 h later and expression at the injection site quantified. Lipid 10, ALC-0315, and SM-102 showed similar expression at the injection site, all greater than the older generation benchmarks lipids (DLinDMA, KC2, MC3). Lipid 10 and ALC-0315 also showed high expression in the liver, while SM-102 was less, and more similar to MC3.Lipid 10-based LNP reported similar anti-HA IgG titers to MC3 and ALC-0315 (Comirnaty) LNP, and higher than the SM-102 (SpikeVax) LNP composition. MCP-1 levels were generally similar, although the ALC-0315 composition had a significantly higher response at the 5 µg dose. All formulations reported good stability when stored frozen at −80 °C or at 2–8 °C for 1 month.

Lipid 2,2(8,8) 4C CH3 is an ionizable cationic lipid (pKa = 6.69).1 It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA in vivo. LNPs containing lipid 2,2(8,8) 4C CH3 and encapsulating siRNA targeting Factor VII decrease plasma Factor VII protein levels by 90% in mice.

TCL053 is a three-tail ionizable lipid studied for local delivery of mRNA and separately encapsulated guide RNA to skeletal muscle in mice. The findings concern the specified research formulation and are not performance specifications for the supplied neat lipid.

NT1-O14B is a tryptamine-containing cationic lipidoid.1 It has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs). Intravenous administration of LNPs containing NT1-O14B and encapsulating antisense nucleotides against tau decreases tau brain levels in mice.

N-[1-(2,3-Dioleyloxy)propyl]-N,N,N-trimethylammonium (DOTMA) is a cationic lipid.It has been used as a component in liposomes that can be used to encapsulate siRNA, microRNAs, and oligonucleotides and for gene transfection in vitro.

Lipid 29 is an ionizable amino lipid (pKa = 6.91) from Moderna platform that has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs).Administration of human erythropoietin (EPO) mRNA in lipid 29-containing LNPs increases serum EPO levels in mice.

DDAB is listed as a ionizable lipid for laboratory research use.

MIC2 is a set of multi-charged lipids with four tertiary amino nitrogen atoms (4N4T) which could be constructed and applied to form novel lipid nanoparticles developed by Westgen. 4N4T-LNPs based on MIC2 exhibit much higher mRNA translation efficiency than the approved SM-102-LNPs. 4N4T-LNPs are successfully applied to DS mRNA vaccine and the vaccines worked well against SARS-CoV-2 and its variants, including Delta and Omicron.

CL4F8-6 is an ionizable cationic lipid (pKa = 6.14) that has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs).1 LNPs containing CL4F8-6 and encapsulating an mRNA reporter accumulate specifically in the mouse liver after intravenous administration. LNPs containing CL4F8-6 and encapsulating mRNA encoding the Cas9 nuclease (mCas9) and single-guide RNA (sgRNA) targeting Ttr (sgTtr), the gene encoding transthyretin, have been used to induce CRISPR-mediated gene knockdown in mice resulting in a reduction of serum levels of TTR.

ALC 0366 is an ionizable cationic lipid (pKa = 6.25) from Biontech,which is derived from ALC-0315. ALC0366 has been used as a key component of LNP to deliver BNT142, a lipid nanoparticle (LNP)-formulated RNA (RNA-LNP) encoding a T cell-engaging bispecific antibody that monovalently binds the T cell marker CD3 and bivalently binds claudin 6 (CLDN6), an oncofetal antigen that is absent from normal adult tissue but expressed on various solid tumors.

Lipid 331 is a biodegradable cyclic ionizable lipid. LNPs containing Lipid 331 result in robust transfection in the nasal and lung tissues of mice and efficient transfection of lung epithelial cells and lung-resident APCs. Lipid 331 is a promising candidate for mRNA vaccine delivery, offering the potential for further enhancing the potency of mRNA vaccines.

76-O17Se is a selenium-containing lipidoid investigated for intracellular delivery of mRNA and genome-editing proteins. In CAR-T cell engineering studies, 76-O17Se-based lipid nanoparticles delivered N1-methylpseudouridine-modified anti-CD19 CAR mRNA into CD8+ T lymphocytes. The resulting CAR-T cells demonstrated cytotoxic activity against B-cell lymphoma cells in vitro, supporting its application in nonviral mRNA delivery and transient immune-cell engineering research.

9322-O16B is a lipidoid for the efficient delivery of antiCD19 mRNA CAR to murine primary macrophages. LNP 9322-O16B is more efficient than delivery with lipofectamine 2000 (LPF2K) or MC3.

Lipid C14-A1 is an ionizable lipid. C14-A1-LPN is a potent and safe LNP platform to deliver Foxp3 mRNA to CD4+ T cells to engineer immunosuppressive FP3T cells.

Lipid C12-A1 is an ionizable lipid. C12-A1-LPN is a potent and safe LNP platform to deliver Foxp3 mRNA to CD4+ T cells to engineer immunosuppressive FP3T cells. C12-A1 has a slightly lower average cell viability than C14-A1.

4A3-SCC-10 is a disulfide bond-containing biodegradable ionizable cationic lipid (pKa = 6.22) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA in vitro and in vivo. LNPs containing 4A3-SCC-10 and encapsulating a Cy5-RNA reporter have improved endosomal escape ability over Cy5-RNA-encapsulated LNPs containing 4A3-SC-10, which does not contain disulfide bonds, in HeLa cells. Intravenous administration of LNPs containing 4A3-SCC-10 and encapsulating an mRNA luciferase reporter selectively accumulate in mouse liver.

4A3-SCC-PH is a groundbreaking linker-degradable ionizable lipid (LDIL) that features a glutathione (GSH)-responsive cone-shaped molecular structure. This unique architecture enables superior endosomal escape and rapid mRNA release, making it highly effective for mRNA delivery. In vivo studies have highlighted its exceptional performance, showing a 176-fold increase in mRNA delivery efficiency to the liver compared to DLin-MC3-DMA, a widely used benchmark lipid. Both 4A3-SCC-PH and its structural analog, 4A3-SCC-10, also demonstrated significantly enhanced mRNA delivery efficacy compared to their non-disulfide-containing parent compounds and disulfide-containing controls with modified lipid tails.

Iso-A11B5C1 is an ionizable lipid. The iso-A11B5C1 LNP demonstrates a high level of muscle-specific mRNA delivery efficiency. exhibiting transfection efficiency comparable to the commercially available lipid SM-102, while considerably reducing inadvertent mRNA expression in main organs such as the liver and spleen.Additionally, study results show that intramuscular administration of mRNA formulated with iso-A11B5C1 LNP caused potent cellular immune responses, even with limited expression observed in lymph nodes.

C18 NC-TNP is a novel noncationic thiourea lipid without positively charged groups. It binds nucleic acids via hydrogen bonds instead of electrostatic attraction, avoiding cation-triggered systemic inflammation. Formulated into nanoparticles, it efficiently encapsulates mRNA, siRNA and plasmids, shows excellent serum tolerance and long-term liquid/lyophilized storage stability. It enters cells mainly through macropinocytosis, escapes endosomes intact to reduce nucleic acid degradation. In vivo, it targets spleen preferentially, induces robust long-lasting Th1-type cellular and humoral immunity with minimal organ toxicity, superior to SM102 LNPs for mRNA cancer vaccine delivery.

200Oi10 is a highly potent, biodegradable ionizable lipidoid optimized for targeted mRNA delivery, with its organ tropism dynamic to the route of administration. Under intravenous injection, it demonstrates an extraordinary 97.7% liver specificity mediated by endogenous ApoE binding. Strikingly, shifting to intraperitoneal injection redirects its tropism, yielding up to 46.4% pancreatic targeting, which can be further boosted when co-formulated with DOTAP. Featuring ester-conjugated cleavable tails, 200Oi10 guarantees rapid metabolic clearance and negligible tissue accumulation toxicity, making it an exceptional candidate for localized pancreatic therapy and efficient hepatic gene delivery.

514O6,10 is an ionizable lipidoid. 514O6,10 formulated LNPs facilitate mRNA delivery to the pancreas.

GVS-18-B6 is a silicon ether-based ionizable lipid (pKa:6.15) developed by Genevant, optimized for mRNA-LNP delivery, characterized by a short-chain trialkyl structure with three C10 alkyl chains (including a cis double bond) and a dimethylamino (DMA) head group linked via a 4-carbon spacer (pKa ~6.15). Its LNP formulations exhibit a narrow particle size distribution (89 nm, PDI=0.06), high mRNA encapsulation efficiency (90%), and pH-dependent surface charge (−0.11 mV at pH 7.5 vs. +2.69 mV at pH 5.5), facilitating endosomal escape. ​​In vivo​​, GVS-18-B6 demonstrated superior liver-specific mRNA expression (5.30×10⁷ pg EGFP/g liver, 2.6× higher than MC3) with minimal spleen accumulation (liver/spleen ratio 92:1 vs. MC3’s 10:1), attributed to rapid non-enzymatic hydrolysis of its silicon ether bonds. This mechanism enables near-complete hepatic clearance within 6 hours in mice and 24 hours in NHPs, avoiding long-term organ retention (MC3 retained 25% in liver after 28 days). Compared to benchmarks (MC3, SM-102, LP-01), GVS-18-B6 showed enhanced potency in RBC hemolysis assays (pH 6.2), indicating earlier endosomal membrane disruption, and maintained stability through 12-month frozen storage or repeated freeze-thaw cycles. ​​Toxicity profiling​​ revealed minimal immunogenicity (MCP-1 levels 0.58×10⁶ vs. MC3’s 1.10×10⁶) and no ALT/AST elevation or anti-PEG antibody induction in NHPs after repeated dosing. Its species-agnostic clearance, low off-target effects, and high tolerability (6 mg/kg dose in mice) position GVS-18-B6 as a leading candidate for chronic disease therapies requiring frequent mRNA administration.

U-101 is an ionizable lipid for mRNA delivery. U101-LNP/IL-2F mRNA formulation demonstrats effective antitumor activity and safety.LNPs containing lipid U 101 and encapsulating mRNA encoding a fusion protein composed of IL-2, a linker, and CD25 inhibit tumor growth in an MC-38 mouse xenograft model.

Lipid B3 is a biodegradable ionizable lipid for liver targeted delivery. Lipid B3-LNP shows high delivery efficacy and low toxicity in delivering RNA to liver cells.

Lipid 119-23 is an ionizable lipid for mRNA delivery. 119-23 LNP exhibits an enhanced capability to express functional mCre in several categories of immune cells, spanning the liver, spleen and lung.

Acid-degradable Cationic Lipid (ADC) composed of cationic lipid is synthesized with the azido-acetal linker and used to generate RD-LNPs, which significantly improves the performance of LNP-mRNA complexes in vitro and in vivo.

ADA (Acid-Degradable Anionic Lipids) is revolutionizing mRNA delivery with its unique azido-acetal linker, enabling rapid hydrolysis in endosomes (pH ~6.0). This breakthrough technology ensures efficient endosomal escape, significantly enhancing mRNA delivery to target cells. ADA-LNPs excel in delivering mRNA to the spleen and liver, making them ideal for immune-related therapies.By degrading into biocompatible byproducts, ADA minimizes long-term tissue persistence and toxicity.ADA-LNPs outperform traditional LNPs, delivering mRNA more effectively to immune cells like macrophages and B cells.

Si5-N14 is a lipid-based molecule engineered with siloxane groups, designed specifically for efficient mRNA delivery to the lungs. The incorporation of siloxane units boosts the cellular uptake of mRNA-loaded lipid nanoparticles (LNPs) and enhances their ability to escape from endosomes. These properties significantly increase the overall effectiveness of mRNA delivery, making Si5-N14 a promising tool for targeted therapeutic applications.

LIPID168(pKa ~6.5) ​​ is an optimized ionizable lipid engineered for in vivo mRNA delivery to hematopoietic stem cells (HSCs) in bone marrow. Developed by ​​Yoltech Therapeutics​​ through high-throughput screening of lipid libraries, it features a ​​diethylamino head group​​ and a tailored hydrophobic tail structure that enables antibody-free targeting. When Lipid 168 was formulated into lipid nanoparticles (LNPs), it achieved ​​48.5% base editing efficiency​​ in bone marrow cells —surpassing benchmarks like LIPID-028 (19.7%)—and reduced off-target liver editing from 71% to 19% by incorporating ​​miR-122 target sequences​​. In humanized β-thalassemia models, LNP 168 delivered ABE8e mRNA/sgRNA to patient-derived HSCs, yielding ​​42.6% editing at the HBG promoter​​, reactivating fetal hemoglobin (γ-globin) and rescuing erythroid defects . Its bone marrow specificity is driven by a unique ​​protein corona​​ enriched in albumin, fibronectin, and fibrinogen . Safety studies confirmed transient immune responses and no cumulative toxicity . LIPID-168 represents a promising non-viral platform for curative gene therapies in blood disorders.

A4B4-S3 is a novel biodegradable ionizable lipid that has been meticulously designed through modular platforms and optimized specifically for mRNA delivery. It serves as a critical component of lipid nanoparticles (LNPs) and enhances mRNA delivery efficiency by facilitating endosomal escape. The structural design of A4B4-S3 leverages the Passerini reaction, a highly efficient and modular chemical method that enables the rapid generation of diverse lipid libraries. The design focuses on optimizing the methylene units between lipid headgroups and linkages to strengthen hydrogen bonding interactions with mRNA ribophosphate complexes. This enhanced hydrogen bonding allows for more effective release of mRNA from endosomes, thereby boosting delivery efficiency. Concurrently, the structural optimization improves biodegradability, reducing potential long-term toxicity risks. In experimental studies, A4B4-S3 has demonstrated superior gene editing efficacy in mouse liver compared to SM-102, a clinically prevalent lipid used in Moderna's COVID-19 vaccine. It also shows potential for repeat-dose protein replacement therapies, suggesting enhanced stability and safety for long-term treatment regimens. Technologically, A4B4-S3 not only provides a more efficient LNP formulation but also deepens the understanding of the relationship between structure and delivery efficiency. This offers new directions for the development of future mRNA therapeutics. In summary, A4B4-S3 represents a next-generation delivery carrier achieved through rational design and high-throughput screening strategies. Its performance enhancements and biodegradable properties position it as a promising candidate for gene therapies and vaccine applications.

SM-86 Analog-1 is a novel ionizable lipid designed to improve the delivery of RNA via lipid nanoparticles (LNPs) It is derived from SM-86,with 8 carbon within its hydrophobic tail.

F10T5 is a furan-derived ionizable lipid developed for mRNA delivery to the central nervous system through the meningeal lymphatic pathway. Its architecture incorporates an ionizable polyamine region and four hydrophobic tails containing acid-sensitive acetal linkages. Following subcutaneous administration near the deep cervical lymph nodes, F10T5 LNPs enabled functional mRNA expression in neurons, microglia, and astrocytes while producing relatively low signals in peripheral organs. Cre mRNA delivery resulted in tdTomato expression in approximately 8.93% of neurons, 7.0% of microglia, and 9.9% of astrocytes in mice. Compared with the co-lead lipid F11T6, F10T5 showed comparable total brain luciferase expression, stronger astrocyte transfection, and lower peripheral-organ distribution. Its activity was associated primarily with improved endosomal escape rather than increased cellular uptake. F10T5 remains a preclinical research lipid, and its repeat-dose safety, pharmacokinetics, and performance in larger animals require further evaluation.

H7T4-4 is an ionizable lipid designed for mRNA delivery via lipid nanoparticles (LNPs). It features a cyclic amine headgroup (derived from cyclen tetrahydrochloride) and four C14 hydrophobic alkyl tails, synthesized through a Michael addition reaction between cyclen and 1,2-epoxytetradecane. With a high transition temperature (Tm = 58.6°C) due to strong intermolecular interactions from its cyclic headgroup and multi-tail structure, H7T4-4 alone forms rigid aggregates incompatible with mRNA encapsulation. However, when blended with low-Tm helper lipids (e.g., DOPE, Tm = -16°C), the system’s overall Tm decreases, enabling stable LNP formation. Optimized formulations (20% H7T4-4, 41% DOPE, 38% cholesterol, 1% DMG-PEG) exhibit efficient mRNA encapsulation (>90%) and transfection. Structural analyses (SAXS, cryo-TEM) confirm monodisperse LNPs with lamellar/hexagonal phases. In vivo, H7T4-4 LNPs show tumor-targeted and intranasal mRNA delivery with reduced off-target accumulation compared to SM-102-based LNPs. This rational design highlights Tm-guided helper lipid selection to overcome rigidity challenges in ionizable lipids.

CF3-2N6-UC18​​ is a rationally designed chloroquine-inspired ionizable lipid that enables robust mRNA delivery and genome editing. It integrates three modular components: a 7-trifluoromethyl-substituted quinoline scaffold (mimicking chloroquine’s endosomolytic properties), a hexamethylenediamine linker with two ionizable nitrogen atoms (pH-responsive protonation), and two unsaturated oleyl (C18:1) hydrophobic tails (enhancing membrane fusion and nanoparticle stability). This lipid self-assembles into ecoLNPs (endosomolytic chloroquine-like lipid nanoparticles) with spherical morphology (~200 nm diameter, 98% mRNA encapsulation). Its pH-sensitive activity triggers endosomal escape through dual mechanisms: ​​proton sponge effect​​ (buffering endo-lysosomal pH) and ​​saposin B-mediated membrane disruption​​ (molecular docking confirms chloroquine-like binding to lysosomal saposin B). In vitro, ecoLNPs outperform commercial reagents (18.9-fold higher mRNA delivery than Lipofectamine 2000) and penetrate 3D cell models. They resist serum/RNase degradation and retain >90% activity after 7-day storage at 4°C. In vivo, ecoLNPs achieve tissue-specific mRNA expression via multiple routes (intravenous, intramuscular, etc.), with strong lymph node tropism (90.2% after intramuscular injection) comparable to SM-102 LNPs (Moderna’s COVID-19 vaccine carrier). They mediate efficient Cre mRNA-driven recombination and CRISPR-Cas9 editing in transgenic mice. CF3-2N6-UC18’s modular design, stability, and dual endosomal escape strategies position it as a versatile platform for mRNA vaccines, gene therapy, and genome editing applications.

Lipid 854 is an ionizable cationic lipid that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA in vivo. Lipid 854 has been optimized based on Lipid 88.

DMA4-H228 is a novel, biodegradable lipidoid specifically engineered for spleen-targeted mRNA delivery.​​ Its structure combines a dimethylamino (DMA4) headgroup with a unique hyperbranched lipid tail (H228) synthesized via Michael addition, incorporating ester bonds for enhanced biodegradability. This design enables the formation of stable lipid nanoparticles (LNPs) (~170 nm) with high mRNA encapsulation efficiency (>96%). Critically, DMA4-H228 exhibits exceptional intrinsic tropism for the spleen (>98% targeting efficiency after IV administration), requiring no external targeting ligands. It selectively delivers mRNA to splenic antigen-presenting cells (APCs), including dendritic cells, macrophages, and B cells. This triggers potent immune activation: rapid IFNα secretion, upregulation of APC maturation markers (CD86/CD40), and robust antigen-specific immune responses. Demonstrating significant therapeutic potential, DMA4-H228-based mRNA vaccines effectively inhibit tumor growth in melanoma models (e.g., B16F10-OVA). This correlates with increased tumor-infiltrating CD8⁺ T cells, a shift towards pro-inflammatory M1 macrophages, elevated antigen-specific antibodies (IgG), and strong T cell responses (evidenced by IFNγ⁺ spots). Its ability to bypass liver tropism and directly activate splenic APCs makes DMA4-H228 a powerful platform for next-generation mRNA vaccines and cancer immunotherapy.

Lipid A-12 is an ionizable cationic lipid from Capstan Therapeutics and a close analog of CICL-1 (L829). The structure was modified by the extension of the headgroup linker from a two-carbon (C2) to a three-carbon (C3) spacer compared to CICL-1 (L829).

TE AA3-Dlin is an optimized lipid nanoparticle (LNP) carrier designed for mRNA-based cancer immunotherapy, enabling precise in vivo dendritic cell (DC) reprogramming to enhance antitumor immunity. TE AA3-Dlin LNP exhibits superior serum stability, maintaining consistent particle size and low turbidity under physiological conditions, while protecting mRNA from degradation, which is crucial for effective delivery. Functionally, TE AA3-Dlin preferentially targets splenic DCs by leveraging ApoE-enriched protein coronas, facilitating efficient cellular uptake and mRNA expression, as demonstrated by enhanced EGFP signals in DCs.This targeting promotes DC maturation, antigen presentation, and membrane-bound IL-15 expression, activating cytotoxic T lymphocytes (CTLs) for tumor rejection. In models like melanoma and colon carcinoma, it synergizes with checkpoint inhibitors, showing minimal toxicity and robust immunological memory.

BHD-C2C2-PipZ, as an efficient ionizable cationic lipid, achieves high encapsulation efficiency and controllable release of mRNA through its unique chemical structure. In PEG-free 3P-LNPs, its electrostatic interaction with tripolyphosphate successfully replaces the steric stabilization effect of traditional PEG, offering a new strategy to circumvent PEG immunogenicity. Its hepatic distribution pattern further indicates that LNP design should take into account the heterogeneity of the organ microenvironment.

C14-306 is a rationally designed ionizable lipid for brain targeting delivery, characterized by a linear 3,3'-diamino-N-methyldipropylamine (306) core conjugated with tetradecyl (C14) tails. This specific architectural configuration, synthesized via epoxide ring-opening amination, yields a molecular structure that optimally balances hydrophobic character and protonation capacity. The C14 alkyl chains enhance membrane integration and LNP stability, while the multiamine core facilitates efficient mRNA complexation and pH-dependent endosomal disruption. When formulated into LNPs with standard helper lipids (DOPE, cholesterol, DMG-PEG2000), C14-306-based nanoparticles exhibit favorable physicochemical properties, including a monodisperse size distribution near 110 nm and high mRNA encapsulation efficiency (>84%). High-throughput in vivo barcoding screening identified C14-306 LNPs as lead candidates for brain delivery, demonstrating a significant tropism for neuronal cells over liver tissue. In validation studies, LNPs incorporating C14-306 achieved a 6.9-fold increase in luciferase mRNA transfection in the mouse brain compared to the SM-102 benchmark, coupled with a substantial reduction in hepatic off-target expression. Flow cytometry confirmed preferential transfection of NeuN+ neurons, and safety assessments indicated no significant blood-brain barrier compromise or induction of systemic inflammation. The efficacy of C14-306 is attributed to its tailored pKa, promoting extended circulation and enhanced endosomal escape within brain cells. C14-306 represents a promising platform for systemic mRNA therapeutics targeting neurological disorders.

AA76-lipid is a dipeptide-modified ionizable lipid, engineered with an arginine-histidine motif, that constitutes the core of the pancreatic-targeted AH-LNP delivery platform. Its chemical architecture, characterized by an externally positioned and C-terminally modified arginine residue, was identified through systematic screening as the optimal structure for function. Upon intraperitoneal administration, AH-LNPs formulated with this lipid interact with proteins in the peritoneal fluid, undergoing dynamic assembly into significantly larger complexes. This substantial increase in size (from ~100 nm to over 360 nm) exploits a physical targeting principle termed the Capsule-filter-mediated pancreatic targeting (CAMP) mechanism. Large particles are selectively filtered out by the dense capsules of other abdominal organs, leading to preferential enrichment in the capsule-deficient pancreas. Concurrently, the arginine-histidine motif directs the formation of a distinct protein corona enriched with apolipoproteins (e.g., APOE, APOB-100), which mimics very-low-density lipoprotein (VLDL). This corona enables efficient cellular internalization primarily into pancreatic stromal cells via VLDL receptor (VLDLR)-mediated endocytosis, known as the VMP pathway. The synergistic integration of the physical CAMP targeting and the biological VMP uptake mechanisms empowers AA76-lipid-based AH-LNPs to achieve highly specific, potent, and sustained mRNA delivery and gene editing within the pancreas across multiple species, demonstrating exceptional therapeutic efficacy in models of both autoimmune pancreatitis and pancreatic cancer.

H5T5 is a leading ionizable lipid nanoparticle (LNP) formulation optimized for in vivomRNA delivery, featuring a pKa of 6.51, a size of ~154 nm, and a narrow polydispersity index (PDI) of 0.05. It demonstrated superior in vitromRNA transfection efficiency in primary immune cells, such as bone marrow-derived macrophages. Following intravenous administration, H5T5 exhibits precise organotropism, predominantly targeting the spleen and bone marrow, where it effectively delivers mRNA to a broad spectrum of immune cells, including macrophages, dendritic cells, T cells, B cells, and NK cells. This capability enables its core application: the in vivogeneration of "pan-CAR" immune cells. When loaded with anti-HER2 CAR mRNA, the H5T5-based therapy achieved potent tumor regression and prolonged survival in multiple solid tumor models. Preliminary safety assessments indicated a manageable cytokine profile and no significant organ toxicity, positioning it as a promising platform for in vivocell engineering.

Lipid 2306 is a novel ionizable lipid developed by Sail Biomedicine demonstrates excellent performance with a spleen-to-liver ratio of 3.68 and a very high total expression level of 2.5E+07. Lipid 2306 offers a strong balance of efficient systemic protein production and clear preferential delivery to the spleen.

Lipid 2310 is a novel ionizable lipid developed by Sail Biomedicine demonstrates excellent performance with a spleen-to-liver ratio of 5.58 and a very high total expression level of 1.3E+07. Lipid 2310 offers a strong balance of efficient systemic protein production and clear preferential delivery to the spleen.

P3B is a biodegradable ionizable lipid engineered to function as a highly efficient delivery vehicle for genome-editing machinery (e.g., CRISPR-Cas9 and adenine base editors) specifically to the central nervous system (CNS). Its primary function is to encapsulate and transport large mRNA payloads across the brain-CSF interface following intrathecal administration, enabling robust and widespread gene editing in neurons and astrocytes across multiple brain regions, including the hippocampus, cortex, and thalamus. Notably, it facilitates precise single-nucleotide correction via base editing. Its targeting is intrinsically achieved by the intrathecal injection route, which localizes the nanoparticles within the cerebrospinal fluid, coupled with an optimized formulation that promotes efficient uptake and activity within CNS parenchyma while minimizing off-target exposure in peripheral organs.

AO12 is a novel antioxidant ionizable lipid derived from SM-102 skeleton with para-hydroxyphenyl propionic acid side chains. Integrated into LNPs, it efficiently scavenges diverse reactive oxygen species including ·OH and ONOO⁻, shielding encapsulated mRNA from oxidative degradation. It retains fine LNP formulation features and cellular uptake capacity of conventional lipids, boosting in vivo mRNA translation. Applied for regenerative mRNA therapy and CRISPR gene editing against fibrosis and inflammatory disorders.

Ionizable lipid-2 is a cationic lipid for nucleic acid delivery, with the ability to form lipid nanoparticle mRNA vaccines that exhibit in vitro stability and immunostimulatory activity.This ALC-0315 analogue retains its ionizable tertiary amine, hydroxybutyl headgroup, and dual branched hydrophobic tails, while replacing the two ester linkages with carbonate groups. This modification may alter hydrolytic stability, biodegradability, membrane interactions, and overall LNP delivery performance.

Ionizable lipid-3( SM-102 analogu) is a cationic lipid for nucleic acid delivery, with the ability to form lipid nanoparticle mRNA vaccines that exhibit in vitro stability and immunostimulatory activity.This SM-102 analogue retains the ionizable tertiary amine and asymmetric hydrophobic architecture while replacing the ester linkages with carbonate groups and repositioning the hydroxyl functionality. These modifications are designed to tune biodegradability, membrane interactions, and LNP delivery performance.

D-Lin-MC4-DMA(MC4) is a cationic lipid that has been synthesized for Lipid nanoparticles (LNPs) to deliver the siRNA.

D-Lin-MC2-DMA(MC2) is a cationic lipid that has been synthesized for Lipid nanoparticles (LNPs) to deliver the siRNA.

AA-T3A-C12 is a leading anisamide-tethered lipidoid (AA-lipidoid) identified through a combinatorial library screening for targeted RNA delivery to activated fibroblasts, offering a promising approach to treat liver fibrosis.AA-T3A-C12 is a leading anisamide-tethered lipidoid (AA-lipidoid) identified through a combinatorial library screening for targeted RNA delivery to activated fibroblasts, offering a promising approach to treat liver fibrosis. It is synthesized via a one-pot, two-step modular method that combines anisamide—a ligand for sigma receptors overexpressed on activated hepatic stellate cells (HSCs)—with a T3A polyamine core and C12 epoxide tails, enabling efficient siRNA encapsulation in lipid nanoparticles (LNPs). In vitro, AA-T3A-C12 LNPs exhibit enhanced cellular uptake and gene silencing in activated fibroblasts, dependent on sigma receptor binding, as confirmed by haloperidol blockade studies, and outperform non-targeted analogs and the FDA-approved MC3 LNPs in fibroblast selectivity.In a mouse model of CCl4-induced liver fibrosis, AA-T3A-C12/siHSP47 LNP achieves approximately 65% knockdown of heat shock protein 47 (HSP47), a key fibrotic target, leading to significant reduction in collagen deposition and fibrosis alleviation, with a good safety profile and no exacerbation of liver injury.

ALC-0315 analogue-2 is an analogue of ALC-0315. ALC-0315 is an ionisable aminolipid that is responsible for mRNA compaction and aids mRNA cellular delivery and its cytoplasmic release through suspected endosomal destabilization. ALC-0315 can be used to form lipid nanoparticle (LNP) delivery vehicles. Lipid-Nanoparticles have been used in the research of mRNA COVID-19 vaccine.

A2-Iso5-4DC19 is a lipidoid compound. A2-Iso5-4DC19 is an effective carrier for the delivery of an agent such as a polynucleotide to a cell.

Lipid 15 is an ionizable amino lipid used for the generation of Lipid nanoparticles .

ALC-0315 analgous-3 is an butanolamine ionizable lipid with both ester bonds located adjacent to C8 relative to the amine head. The introduction of ester linkages can improve the clearance of the lipid in the liver. This compound is analgous to ALC-0315.

BP Lipid 114 is a well-designed ionizable lipid optimized for mRNA encapsulation and delivery. Its ethanolamine headgroup, ester bonds at the C6 and C8 positions, and 9-carbon tail contribute to efficient mRNA complexation, stability during delivery, and improved biodegradability. These properties make it a valuable component in LNPs for gene therapy and other mRNA-based therapeutic applications.

BP Lipid 135 is a well-designed ionizable lipid optimized for mRNA encapsulation and delivery. Its propanolamine headgroup, ester bonds at the C8 position, and 9-carbon tail contribute to efficient mRNA complexation, stability during delivery, and improved biodegradability. These properties make it a valuable component in LNPs for gene therapy and other mRNA-based therapeutic applications.

Acuitas Lipid III-2 is an ionizable amine lipid with two identical ester tails adjacent to C6 position relative to amine from patent:WO2017075531A1 with the similar activity as ALC-0315. The head of lipid is propanolamine which can effectively encapsulate mRNA used in gene therapies which depends on the availability of a safe and efficient delivery vehicle.

An analog of SM-102. The ethanolamine amino lipid head enhances encapsulation of mRNA. The lipid has primary esters at C7 position relative to the amine nitrogen. The primary lipid tail has 8 carbon tail. The lipid can be used for mRNA-based therapies which depends on the availability of a safe and efficient delivery vehicle.

RCB-4-8​​ is a biodegradable ionizable lipid nanoparticle (LNP) engineered for efficient pulmonary mRNA delivery and in vivo genome editing, as detailed in the primary research article ​​"Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing"​​ (Li et al., Nature Biotechnology 2023）. Synthesized from a combinatorial library of 720 biodegradable lipids via a three-component reaction system, RCB-4-8 features an alkyne-containing lipid tail and tertiary amine headgroup, optimized through high-throughput screening for superior lung-targeting capabilities. Its unique molecular design incorporates hydrolyzable ester and carbonate groups, enabling rapid biodegradation (<30% lung retention at 48 h vs. >90% for conventional lipids) while maintaining high transfection efficiency. When formulated with DOTAP instead of DOPE, RCB-4-8 LNPs achieved ​​100-fold higher luciferase mRNA expression​​ in murine lungs compared to FDA-approved MC3 LNPs and mediated ​​95% GFP knockout​​ in vitro. In Ai9 reporter mice, intratracheal delivery of RCB-4-8 loaded with Cre mRNA edited ​​53% of total lung cells​​ after three doses, while codelivery with Cas9 mRNA/sgRNA yielded ​​7.2% tdTomato+ cells​​, rising to ​​17%​​ when combined with AAV-sgRNAs. With an optimal particle size of ​​85.7 nm​​ (PDI 0.11) and ​​>87% mRNA encapsulation​​, RCB-4-8 supports repeat dosing and represents a transformative platform for inhalable gene therapies targeting congenital lung diseases like cystic fibrosis.

L-369 (Lipid 369,L369) is novel class of ionizable lipid for siRNA delivery with improved in vivo elimination profile with excellent translation across species,including NHP, wide safety margin.

VL-422 is an ionizable cationic lipid. VL-422 delivers CRISPR complementary single-guide RNA (sgRNA) and Cas9 mRNA to enable in vitro and in vivo gene editing. LNPs containing VL-422 loaded with Cas9 mRNA and sgRNA targeting the ANGPTL3 gene induce the deletion of premature stop codons within the ANGPTL3 gene in the liver of cynomolgus monkeys. Loss-of-function of ANGPTL3 leads to decreased levels of LDL, HDL and cholesterol in plasma. The VL-422 delivery system can be used for the research of gene editing strategies targeting lipid metabolism diseases.

CL15F6 is an ionizable cationic lipid (pKa = 6.75).1 It has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA and polymer-lipid hybrid nanoparticles for the delivery of plasmid DNA in vitro.1,2

Lipid88​​ is a high-performance, novel ionizable lipid component engineered for advanced mRNA-LNP vaccine delivery. LNP88 formulation demonstrates superior biodistribution, achieving >10-fold higher transfection efficiency in spleen and lymph nodes compared to benchmark lipids like ALC-0315 via intramuscular delivery. When encapsulating antigen-encoding mRNA (e.g., optimized mCSA construct), Lipid-88 based LNPs drive robust humoral and cellular immunity, enabling complete protection against challenging SARS-CoV-2 variants (WA1/2020, Omicron BA.1, BQ.1) in preclinical models. Its design prioritizes potent immunogenicity with favorable safety profiles.

YSK 12C4 is an ionizable cationic lipid primarily used to enhance siRNA cellular delivery via multifunctional envelope-type nanodevices (MEND). YSK 12C4 promotes siRNA uptake and endosomal escape, effectively silencing genes in human immune cell lines.

Lipid 29 analogue-2 is an ionizable lipid designed for the delivery of RNA-based therapeutics, such as mRNA or siRNA.

Acuitas Lipid III-25 is an novel ionizable amine lipid used for mRNA delivery from Acuitas Therapeutics patent US 10,166,298 B2, with pKa 6.22, Liver Luc 1648 for 0.3mgkg(ng luc/g liver), Liver Luc 13880 for 1mgkg(ng luc/g liver) . It is an analgous of ALC-0315, showing higher activity than ALC-0315.

Acuitas II-12 is an novel ionizable amine lipid used for mRNA delivery from Acuitas Therapeutics patent WO2016176330A1

Acuitas Lipid III-7 is an novel ionizable amine lipid used for mRNA delivery from Acuitas Therapeutics patent US 10,166,298 B2.

Moderna Lipid 26（Lipid M） is an ionizable cationic lipid (pKa = 6.75) that has been used in the generation of lipid nanoparticles (LNPs) for mRNA delivery in vivo. LNPs containing lipid M and encapsulating mRNA encoding influenza virus genes increase anti-influenza virus IgG titers in cynomolgus monkeys without inducing local edema, erythema, or systemic levels of IL-6.

Moderna Lipid 48 is an novel ionizable amine lipid used for mRNA delivery from Moderna patent WO2017049245A2

Moderna Lipid compound 182(Lipid 29 analogue-1) is a novel ionizable amine lipid developed by Moderna for the delivery of mRNA-based therapeutics. This lipid is part of Moderna's proprietary lipid nanoparticle (LNP) delivery platform, which is designed to encapsulate and protect mRNA, facilitate its cellular uptake, and enable efficient intracellular release. The ionizable nature of Lipid Compound 182 allows it to interact with mRNA at low pH (during LNP formulation) and release the payload in the neutral pH environment of the cytoplasm, making it a critical component of Moderna's mRNA delivery system.

Lipid 29 analogue-3 is an ionizable lipid designed for the delivery of RNA-based therapeutics, such as mRNA or siRNA.

IAJD-34 is a one-component ionizable amphiphilic Janus dendrimer specifically engineered for targeted mRNA delivery to the lung parenchyma, as described by Meshanni et al. in Nature Communications article "Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers" . This synthetic nanoparticle self-assembles with mRNA through simple mixing in acetate buffer, forming stable dendrimersomes approximately 93-97 nm in size with high encapsulation efficiency (>95%) and a positive zeta potential (~48 mV). Its defining feature, highlighted in the study, is exceptional lung tropism after intravenous injection, enabling significantly higher luciferase expression in murine lungs compared to other organs. As demonstrated by Meshanni et al., IAJD 34 effectively delivers therapeutic mRNA (e.g., TGF-β mRNA) to the lower lung, inducing transient protein production with minimal systemic toxicity at appropriate doses (e.g., 10 µg), offering a promising strategy for treating parenchymal lung diseases.

TG4C is an ionizable cationic lipid (pKa 6.71) optimized for mRNA delivery via lipid nanoparticles (LNPs). When formulated into LNPs carrying human EPO mRNA, it significantly elevates serum EPO levels in mice. Furthermore, aerosolized TG4C-based LNPs containing HGF mRNA demonstrate therapeutic potential in pulmonary emphysema models, showing reduced inflammatory cytokines (IL-1β, IL-6, TNF-α) in bronchoalveolar lavage fluid after elastase-induced lung injury.

A28-C6B2 is a biodegradable ionizable lipid specifically engineered for spleen-targeted delivery. Through its unique branched structure, it bypasses hepatic uptake to achieve highly efficient transfection of F4/80+ macrophages and CD11c+ dendritic cells within the spleen. This lipid remains neutral in the bloodstream to minimize non-specific interactions, while undergoing protonation in the acidic environment of the endosome to facilitate nucleic acid release, thereby significantly enhancing the potency of mRNA vaccines and immunotherapies.

TD5 is a tryptamine-derived ionizable cationic lipid used to prepare LNPs for mRNA delivery. In the reported formulation, TD5 supported pH-dependent mRNA encapsulation and CNS delivery after intrathecal administration. Reported performance values below remain tied to the stated formulation and study conditions; they should not be compared across methods without reviewing those conditions.

​​DM3-BTA-14​​ is a cationic lipid compound engineered for high-efficiency mRNA delivery developed by Hefei AlphaNA Biotechnology. Its structure features a rigid benzene-1,3,5-tricarboxamide core linked to a protonatable dimethylamino headgroup (-N(CH₃)₂) via a propylene spacer (-CH₂CH₂CH₂-) and two saturated C14 alkyl chains. This design enables ≈90% endosomal escape efficiency , superior lymph node targeting for vaccines , and effective tumor-specific mRNA delivery . It outperforms benchmark lipids while maintaining low cytotoxicity, forming stable nanoparticles with cholesterol/DSPC/DSPE-PEG (50:39:10:1 ratio) for therapeutic applications.

XH-04 ​​is an ionizable lipid engineered for advanced mRNA delivery developed by ​​JiaChen West Lake Biotech. Its core structure features a central benzene ring with asymmetric hydrophobic tails (C9-C10 chains) and pH-responsive tertiary amines that enable efficient mRNA encapsulation and endosomal escape. As detailed in CN113993839A, XH04 outperforms industry benchmarks (e.g., MC3 lipid), boosting protein expression by ​​>10-fold​​ in BHK cells. In PCT/CN2024/121624, JiaChen further demonstrated its utility in lung-targeted LNPs (tLNP/tLCNP). When combined with cationic lipids (e.g., DOTMA at 2:1 molar ratio), XH 04 redirects >80% of mRNA delivery to murine lungs—overcoming liver tropism—while maintaining low toxicity. The lipid’s benzenic core and optimized alkyl chain geometry (patent claims 1-9) are credited for enhanced endosomal disruption and mRNA release kinetics. JiaChen’s innovations position XH-04 as a cornerstone for next-generation mRNA therapeutics.

CS22021 is a novel, synthetically engineered ionizable sterol lipid (ISL) developed by CanSino, specifically designed for advanced mRNA delivery via lipid nanoparticles (LNPs). Its core innovation lies in its unique molecular architecture, which integrates a cholesterol moiety directly conjugated to a branched aliphatic tail (derived from ALC-0315) and a hydrophilic headgroup containing tertiary amines. This bifunctional design allows CS22021 to simultaneously fulfill the roles of both the ionizable lipid (for mRNA binding/encapsulation and endosomal escape) and the structural cholesterol component within LNPs. Consequently, CS22021 enables the formulation of highly efficient three-component LNPs (ISL-3C-LNPs), eliminating the need for free cholesterol, using only itself, the phospholipid DOPE (crucial for forming stable, uniform nanoparticles without defects), and a PEGylated lipid. When formulated into LNPs and administered intramuscularly, CS22021 demonstrates a critical property: it achieves localized mRNA expression predominantly at the injection site, significantly minimizing off-target delivery (especially to the liver/spleen) and associated systemic toxicity. Furthermore, mRNA vaccines delivered by CS22021-based LNPs elicit robust and balanced immune responses, including strong antigen-specific IgG antibodies and, notably, a significantly enhanced CD8+ T cell response compared to conventional four-component LNPs. This combination of efficient mRNA encapsulation/delivery, localized expression for improved safety, and potent induction of cellular immunity, particularly CD8+ T cells, positions CS22021 as a highly promising lipid platform, especially for next-generation mRNA vaccine applications like cancer immunotherapy.

A5-CE-C7-6 (3-tail analog) is a structural control compound derived from the standard 2-tail lipid(A5-CE-C7-6), with three carbonate alkyl chains linked to the A5 amine core.

Sail Lipid 2231 is a novel ionizable lipid targeting to spleen developed by Sai Biomedicine.As described on US20250205167A1 Lipid 2231 features a ​​pyrrolidine core​​ (5-membered ring) with biodegradable ester linkages and asymmetric C17/C11 hydrophobic chains. In vivo data shows moderate spleen targeting (Spleen RLU: ​​3.8E+06​​) with a spleen-to-liver ratio of ​​12.767​​.

Sail Lipid 2308​ is a novel ionizable lipid targeting to spleen developed by Sai Biomedicine.As described on US20250205167A1, Lipid 2308 was designed with a ​​piperidine core​​ (6-membered ring) and asymmetric C17/C11 chains, this lipid achieves unprecedented ​​spleen-specificity​​. It demonstrates dominant spleen accumulation (Spleen RLU: ​​7.8E+06​​, 91.8% of total signal) with a record ​​spleen-to-liver ratio of 112.7​​ (9× higher than 2231). Despite lower protein expression (hEPO: 11,000 ng/mL), near-zero liver uptake (Liver RLU: 66,000) makes Lipid 2308 unparalleled for vaccine/immunotherapy applications targeting splenic immune cells.

CVL1 (C24), also known as VitE-C4DE-Pip-S, is a vitamin E-derived ionizable lipid developed for lipid nanoparticle-mediated delivery of mRNA and other nucleic acids developed by CureVac. It features two hydrophobic α-tocopherol moieties connected to a bis-piperidine ionizable core through biodegradable succinate ester linkages, while a central thioether-containing spacer provides additional structural flexibility. CVL1 can be incorporated into LNP formulations to support nucleic acid encapsulation, cellular uptake, and intracellular delivery. CureVac has investigated CVL1-containing LNPs for mRNA expression in immune-related tissues and cells, including the spleen, lymph nodes, and antigen-presenting cells, making it a valuable research lipid for mRNA vaccines, cancer immunotherapy, and other nucleic acid delivery applications.

ARV-T1 is a novel ionizable lipid featuring a cholesterol moiety incorporated in its tail, designed to enhance mRNA delivery efficiency. With a pKa of 6.73, it exhibits optimal pH-dependent ionization for endosomal escape and mRNA release. Structurally, ARV-T1 contains a tertiary amine head group and ester-linked lipid tails, enabling rapid in vivo metabolism and improved biocompatibility.Compared to SM-102 (used in Moderna's vaccine), LNPs formulated with ARV-T1 demonstrate superior physicochemical properties: smaller particle size (~80 nm vs. 90 nm), lower polydispersity index (0.09 vs. 0.10), and higher absolute zeta potential (-10 mV vs. -5 mV). These characteristics correlate with >90% mRNA encapsulation efficiency and enhanced stability, maintaining performance for 12 weeks at -20°C.In vitro, ARV-T1 LNPs showed 7-fold higher protein expression than SM-102 LNPs. In vivo, they prolonged luciferase expression (>72 hours vs. <48 hours for SM-102) and induced 10-fold higher neutralizing antibodies against SARS-CoV-2 spike protein at low doses. The cholesterol tail promotes endosomal membrane fusion, while ester linkages facilitate metabolic clearance, yielding an excellent safety profile in toxicity studies. This combination of efficacy and safety positions ARV-T1 as a promising platform for mRNA vaccines and therapeutics.

AX6​​ is an ionizable lipid in the ​​F32 LNP​​ formulation, engineered by ReNAgade/Orna Therapeutics for targeted mRNA delivery to T cells. AX-6's unique ​​bridged bicyclic/polycyclic core​​ with a ​​tertiary amine group​​ enables pH-dependent protonation and endosomal escape, while ​​C14-C18 hydrophobic tails​​ (optionally branched/fluorinated) enhance bilayer stability and mRNA encapsulation. Demonstrating ​​exceptional T-cell tropism​​, AX6 achieves high transfection efficiency in CD4+/CD8+ T cells (validated in NHP/humanized models) with minimal toxicity. Compared to clinical benchmarks (SM-102, ALC-0315), its rigid core offers superior ​​serum stability​​ and ​​immune-cell specificity​​, positioning it as an ideal candidate for ​​CAR-T/NK therapies​​ and ​​next-gen vaccines​​. The F32 LNP system's proven efficacy (e.g., in vivo B-cell depletion) underscores AX 6's transformative potential for ​​cell engineering​​ and ​​immunotherapies​​.

MoChol is a cationic cholesterol derivative used as a membrane component in charge-reversible amphoteric nanoliposomes. It has been incorporated with CHEMS, DOPE and POPC into liposomal formulations for the delivery of anti-BCL-2 antisense oligonucleotides.

EB-Lipid is an innovatively engineered ionizable lipid designed to replace conventional PEG-lipid in mRNA vaccine formulations. Its structure comprises three key components: an Evans Blue-derived headgroup with high affinity for albumin, a tetraethylene glycol linker that enhances colloidal stability, and dual oleate tails for anchoring into lipid bilayers. This molecular design enables EB-Lipid to actively recruit endogenous albumin, forming an albumin-rich protein corona on the surface of lipid nanoparticles (LNPs). Following intramuscular administration, these albumin-bound EB-LNPs are preferentially transported through lymphatic vessels rather than entering the bloodstream, thereby avoiding hepatic accumulation and associated hepatotoxicity risks.Experimental data demonstrate that EB-LNPs achieve significantly higher accumulation in lymph nodes, where they are efficiently internalized by dendritic cells via albumin receptor-mediated endocytosis (e.g., gp60). This process enhances antigen presentation and activates robust cellular and humoral immune responses. In both tumor models (B16-OVA and HPV-associated) and infectious disease models (H1N1 and SARS-CoV-2 Omicron), EB-LNP-based mRNA vaccines elicited potent cytotoxic T-cell activation and durable neutralizing antibody production at low doses. Unlike traditional PEG-LNPs, EB-LNPs show minimal liver distribution, reduced immunogenicity, and improved safety profiles after repeated administrations.By leveraging albumin’s natural trafficking pathway, EB-Lipid represents a transformative delivery platform that combines targeted lymph node delivery with enhanced biosafety, positioning it as a promising candidate for next-generation mRNA vaccines and therapeutics.

CICL-242​ is a constrained ionizable cationic lipid highlighted in patent US 20250127728A1 developed by Capstan as a promising candidate for advanced therapeutic delivery, particularly in stem cell and gene editing applications. Its structure features a rigid amine headgroup similar to CICL-207, which likely facilitates efficient endosomal escape and reduces non-specific uptake, enhancing targeted nucleic acid delivery. Although detailed performance data is not fully disclosed in the patent, CICL-242 is explicitly synthesized and included in gene editing experimental systems (e.g., CRISPR-Cas9 workflows), suggesting its potential for high-efficiency transfection in hard-to-transfect cells​ like hematopoietic stem cells (CD34⁺). This makes it a strong candidate for ex vivo cell engineering and regenerative medicine, where precision and low off-target effects are critical. While further validation is needed to quantify its efficacy and safety profile, CICL-242 represents a strategic innovation in the lipid library for next-generation genetic therapies.

Imidazole cholesterol ester (ICE) is a sterol‑based ionizable cationic lipid invented by Translate‑Bio (WO2018/089790 A1) for mRNA‑loaded lipid‑nanoparticle (LNP) pulmonary delivery. It fuses an imidazole pH‑responsive headgroup with cholesterol via ester linkage. Typically formulated as a three‑component LNP (ICE : DOPE : DMG‑PEG2K = 60 : 35 : 5 mol ratio), ICE‑LNPs achieve high mRNA encapsulation (>80‑90 %), good nebulization stability and low toxicity. Upon cellular uptake, imidazole mediates endosomal escape; the ester bond degrades to yield cholesterol, conferring favorable biocompatibility. Animal studies demonstrate robust CFTR protein expression in bronchial and alveolar lung tissue after inhalation, making ICE promising for cystic‑fibrosis mRNA therapy.

CL15F 6-4 is a short-tail ionizable lipid from the piperidine-based CL15F series, characterized by its symmetric branched structure with a 6-carbon main chain and 4-carbon side chain. This specific tail length critically determines the lipid nanoparticle's (LNP) properties, resulting in larger particles with a high surface density of the phospholipid DSPC. This elevated DSPC density reduces interactions with serum proteins like ApoE, minimizing rapid liver clearance and shifting mRNA delivery preference towards the spleen. Consequently, CL15F 6-4 LNPs achieve efficient, endogenous spleen-targeted delivery, making them a highly promising candidate for enhancing vaccine efficacy by preferentially transfecting antigen-presenting cells without complex functionalization.

KT-001 is a novel ionizable cationic lipid developed by Vivas, Inc., disclosed in US 2026/0007612 A1 (published Jan 8, 2026).KT-001 demonstrates exceptional skeletal muscle targeting and low liver toxicity.Unlike traditional lipids that primarily accumulate in the liver, KT-001 avoids serum ApoE binding, preventing hepatic uptake. Upon intramuscular injection, it achieves a 29-fold reduction in liver off-target expression compared to standard lipids, while maintaining robust, long-lasting protein expression at the injection site.Its optimized pKa enables precise, pH-responsive endosomal escape for high transfection efficiency. KT-001 is an ideal carrier for localized mRNA vaccines and targeted therapeutics for muscle-related disorders.

BiP-20 is a branched ionizable phospholipid identified as a lead compound for efficient hepatic mRNA delivery.BiP-20 is a novel, efficient, and safe liver-targeted LNP delivery vehicle. With an ideal pKa of 6.56, it achieves highly efficient liver targeting and endosomal escape primarily through the ApoE/LDL-R pathway. It demonstrates exceptional performance in gene editing at very low doses: for CRISPR-Cas9-mediated editing of TTR, a 10 μg dose achieved ~64% efficiency, which is 8-fold higher than the clinical benchmark lipid LP-01. In Prime Editing targeting the PCSK9 gene, its efficiency (4.30%) also significantly surpassed that of MC3, SM102, and LPO1. Furthermore, it mediates a 5.9-fold increase in hepatic protein expression compared to MC3. Safety assessments indicate it does not induce liver function abnormalities, showing strong therapeutic potential.

1A7B13 is a top-performing "tripod-like" lung-targeting (LuT) lipid. It forms lipid nanoparticles (LNPs) that, after intravenous injection, deliver genetic medicines (like mRNA and CRISPR-Cas9) to the lungs with over 90% selectivity, particularly favoring epithelial cells. Compared to the benchmark DOTAP LNPs, 1A7B13 LNPs achieve a 25.5-fold increase in mRNA delivery and a 9.2-fold improvement in gene-editing efficiency within the lungs. Its therapeutic potential was demonstrated by successfully delivering IL-10 mRNA to treat acute lung injury in mice.

Trp-L1-T4 is a novel tryptophan-derived ionizable lipid that serves as the core functional component of the optimized lipid nanoparticle (TLNP/RLNP) platform. Its primary function is to enable the efficient encapsulation and in vivo delivery of self-amplifying RNA (saRNA) cargo. Specifically, it facilitates high transfection efficiency and cytosolic release of the RNA payload in target follicular helper T (Tfh) cells, with minimal cytotoxicity. This capability is crucial for reprogramming pathogenic Tfh cells into regulatory CAR-Tfh cells, forming the foundation of the study's therapeutic strategy.

Lipid A10 (CSS-A10) is a diketopiperazine-core ionizable lipid used in the LNP67 formulation for mRNA delivery to hematopoietic stem and progenitor cells. In the cited study, ligand-free LNP67 delivered reporter mRNA to mouse bone-marrow HSC/HSPC populations and to CD34+ cells in young rhesus monkeys after intravenous administration.

KC-34 (SPC-A9) is a novel stereopure, diketopiperazine-based ionizable cationic lipid engineered to overcome traditional liver-restricted delivery, achieving balanced multi-organ mRNA transfection. Upon systemic intravenous administration, its precisely optimized chiral configuration allows the lipid nanoparticles (LNPs) to efficiently cross endothelial barriers and target the bone marrow, offering immense therapeutic potential for in vivo hematopoietic stem cell gene editing. Concurrently, KC-34 mediates robust and long-lasting protein expression in the spleen and lungs with minimal hepatic off-target toxicity. Its stable structure provides excellent biocompatibility and high in vivo tolerance, making it ideal for systemic, multi-dose mRNA therapies.

L52715 is a novel ionizable lipid developed by Shanghai Vitalgen, used to deliver mRNA.

A5-CE-C7-6 is an ionizable lipid engineered for spleen-targeted mRNA delivery, integrating a hydroxylated dual-amine core (A5) for enhanced mRNA binding and endosomal escape, a biodegradable carbonate ester linker (CE) enabling rapid hydrolysis (61% degradation in 24 h), and branched heptyl hydrophobic tails (C7-6) that optimize nanoparticle stability and spleen tropism.​​ When formulated into cholesterol-free lipid nanoparticles (B-8 formulation), its unique architecture—combining hydroxyl groups for cellular uptake, carbonate-mediated biodegradability, and branched-chain fluidity—achieves unprecedented efficiency: low pKa (~6.0) minimizes liver accumulation while enabling ​​21% transfection of splenic NK cells​​, outperforming benchmark systems like MC3 SORT LNPs by >10-fold in spleen-specific delivery and establishing a new standard for in vivo immune cell engineering.

SM-102 azide is an azide-modified derivative of the clinically validated SM-102 ionizable lipid. Designed specifically for advanced Lipid Nanoparticle (LNP) formulation, this product integrates a reactive azide (-N₃) group to enable effortless, high-yield functionalization via click chemistry. It is the ideal tool for researchers and developers looking to construct targeted nucleic acid delivery systems, build diverse lipid libraries, or track LNPs in vivo.

CSL3 is a pH-switchable cationic lipid optimized for siRNA LNP delivery. Its core design features central pyridine and two ortho-methoxy groups, forming intramolecular hydrogen bonds under endosomal pH 5–6 to trigger conformational flip, which drives membrane fusion and efficient endosomal escape—an advantage absent in control lipid CSL4 without methoxy moieties. Formulated with DSPC, cholesterol and DMG-PEG2000 at a fixed molar ratio, CSL3-based LNPs achieve 85–95% siRNA encapsulation, uniform particle size and decent serum stability. In vitro tests show potent gene silencing with low cytotoxicity; in vivo intravenous administration enables obvious liver accumulation and dose-dependent Factor VII knockdown in mice, proving its great potential for hepatic RNAi therapeutic research.

A3B7C2 is an imidazole-containing ionizable lipid evaluated in a four-component LNP for spleen-selective reporter mRNA expression.

A1B7C2 is an imidazole‑based ionizable lipid from the IMIL library. It features dimethylamino‑propyl imidazole head group, paired with B7 hydrophobic tails and C2 degradable ester linkers. LNPs assembled from A1B7C2 can effectively accumulate within the spleen after systemic administration. It mediates mRNA expression in splenic tissue, and is applied as a key control compound to investigate structure‑activity relationships for spleen‑targeted nucleic acid delivery.

CA2d is an ionizable lipid developed for systemic mRNA delivery to the central nervous system. Its architecture combines an MK-0752-derived CNS-accessing moiety, a short three-carbon diamine spacer, a tertiary ionizable amine, and two acetal-containing hydrophobic tails. When formulated with DOPE, cholesterol and DMG-PEG2000, CA2d LNPs crossed the blood-brain barrier through caveolae- and γ-secretase-associated transcytosis and delivered mRNA to neurons, astrocytes, microglia and brain endothelial cells. Following intravenous administration of FLuc mRNA at 0.5 mg/kg in mice, CA2d produced 16.6-fold higher brain expression than MC3 and 8.6-fold higher expression than SM-102 at 6 hours. CA2d was further evaluated in repeated brain-cell transfection studies, a pilot rhesus macaque experiment and a tPA-modified TGF-β1 mRNA formulation for ischemic stroke. These results support CA2d as a promising preclinical research lipid for investigating non-viral CNS mRNA delivery; it has not been clinically validated.

98N12-5 is an ionizable cationic lipid. It has been used in combination with other lipids in the generation of lipid nanoparticles (LNPs). LNPs containing 98N12-5 and encapsulating proprotein convertase subtilisin kexin type 9 (PCSK9) siRNA selectively accumulate in the liver and reduce total serum cholesterol levels in mice and rats and serum LDL levels in cynomolgus monkeys.

YSK 05 is a pH-sensitive cationic lipid. YSK 05 improves the intracellular trafficking of non-viral vectors. YSK 05-MEND shows significantly good gene silencing activity and hemolytic activity. YSK 05 overcomes the suppression of endosomal escape by PEGylation. YSK 05 effectively enhances siRNA delivery both in vitro and in vivo.

Lipid A6 is an ionizable cationic and biodegradable alkyne lipid (pKa = 6.65).It has been used with other lipids in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA. LNPs containing lipid A6 and encapsulating mRNA encoding human erythropoietin (EPO) increase and then maintain homeostatic levels of hemoglobin in the blood in an adenine-induced mouse model of renal anemia.

113-O12B LNP, an LN-targeting LNP delivery system, is developed for a mRNA cancer vaccine.

306Oi10 is a branched ionizable lipid that can be used to construct lipid nanoparticles (LNPs) for delivering messenger RNA. The surface ionization of lipid nanoparticles is related to the effectiveness of mRNA delivery. The tail of 306Oi10 has a one-carbon branch, which provides it with stronger surface ionization compared to lipids with linear tails, thereby enhancing its mRNA delivery efficacy. 306Oi10 can be used in research related to mRNA delivery.

A2-Iso5-2DC18 is a top-performing lipid for mRNA delivery in bone marrow-derived dendritic cells (BMDCs), BMDMs and HeLa cells.

A18-Iso5-2DC18 that could not only deliver mRNA vaccines robustly but also activate the stimulator of interferon genes (STING) pathway.

OF-C4-Deg-Lin is a novel ionizable lipid for RNA delivery.

4A3-SC8 is a novel Ionizable amino lipid for RNA delivery.The CRISPR-Cas9 gene editing system has been a hotspot in the field of gene therapy, especially the gene correction induced by homology-directed repair (HDR). However, its application has various obstacles, such as large molecular weight, poor stability, off-target risk, and the complexity of codeliver multiple genes. Farbiak et al. established a novel ionizable lipid library consisting of four distinct amine cores (3A3, 3A5, 4A1, 4A3) and nine peripheries with different alkyl chain lengths (SC5-SC14), and screened out a class of iLNPs with ability of encapsulating Cas9 mRNA, sgRNA and donor DNA simultaneously. The delivery efficiency (quantified by luciferase mRNA expression) and iLNPs toxicity were evaluated with three different cell lines (HEK293T, HeLa, and IGROV-1), indicating the formulation containing 4A3-SC8 was the best. 4A3-SC8 iLNPs successfully induced HDR in HEK293 cells by one-pot delivery of Cas9 mRNA, sgRNA, and the correct ssDNA template. Confocal microscopy imaging showed that a portion of blue fluorescence in cells was corrected to green fluorescence. Furthermore, the nucleic acid ratios of Cas9: sgRNA: donor DNA loading in iLNPs at a ratio of 2:1:3 could maximize the HDR efficiency with the editing efficiency up to 23%, which breaks through the current bottleneck of HDR efficiency of only 1–5%. This progress is undoubtedly an important advance in the gene therapy field to cure diseases caused by genetic mutations.

A12-Iso5-2DC18 is a novel amine containing lipid can be used for mRNA delivery, activate the stimulator of interferon genes (STING) pathway, and exhibit anti-tumor immunity.

306-O12B-3 is an ionizable lipidoid with cationic properties, commonly used in lipid nanoparticle (LNP) formulations for antisense oligonucleotide (ASO) delivery. When administered intravenously in mice, LNPs incorporating 306-O12B-3 exhibit liver-specific accumulation. Studies show that ASO-loaded LNPs containing 306-O12B-3 effectively silence hepatic PCSK9 expression by targeting the proprotein convertase subtilisin/kexin type 9 gene. Additionally, when combined with the cationic lipidoid NT1-O14B (Item No. 37095), these LNPs can deliver tau-targeting ASOs to the brain, reducing tau protein levels in mice.

AA3-DLin is an ionizable cationic amino lipid (pKa = 5.8) that has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA.LNPs containing AA3-DLin and encapsulating mRNA for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein induce immunogenicity in mice.

PPZ-A10 is an ionizable cationic lipid.It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA and mRNA in vitro and in vivo. Intraperitoneal administration of LNPs containing PPZ-A10 and encapsulating an mRNA reporter preferentially accumulates in hepatic Kupffer cells and splenic macrophages in mice.

93-O17O is a chalcogen-containing ionizable cationic lipidoid. It has been used in the generation of lipid nanoparticles (LNPs). LNPs containing 93-O17O localize to the spleen after intravenous injection into mice.LNPs containing 93-O17O have been used for the delivery of Cre recombinase and ribonucleoproteins for genome editing in mice and for the intratumoral delivery of cGAMP to enhance cross-presentation of tumor antigens.

BAmP-TK-12 is a ROS-responsive ionizable lipid designed for tumor-cell mRNA delivery. It features a bis(aminopropyl)piperazine-derived ionizable headgroup and four C12 tails connected through cleavable thioketal linkers. In the reported study, BAmP-TK-12 achieved RFP expression in up to 95% of HeLa cells, comparable to Lipofectamine 3000, with lower cytotoxicity under the tested conditions. ROS-triggered linker cleavage supported intracellular mRNA release in high-ROS tumor cells. When formulated with DUF5 mRNA, the LNP suppressed tumor growth in HCT-116 and A549 xenograft models, supporting its use as a promising preclinical research lipid for stimulus-responsive mRNA delivery.

113-O16B is a disulfide bond-containing ionizable cationic lipidoid. It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA.

LIPID 14 is a novel ionizable lipid used for mRNA delivery.In 2021, Elia et al. used lipid 2 LNPs and lipid 14 LNPs to deliver mRNA encoding SARSCoV-2 human Fc-conjugated receptor binding domain (RBDhFc mRNA). While both lipid 274 LNP RBD-hFc mRNA and lipid 14 LNP RBD-hFc mRNA induced equal cellular and humoral responses in mice at an mRNA dose of 5 μg, only lipid 14 LNP RBD-hFc mRNA exhibited strong immunogenicity following intradermal administration. Both intradermal administration and intramuscular administration of lipid 14 LNPs could activate antigen presenting cells (APCs), thus inducing cellular responses.

Lipid 10a-26​​ is an ionizable lipid developed by Orna Therapeutics for lipid nanoparticle (LNP) formulations. Lipid 10a-26 is a key ionizable lipid in the LNP-6 formulation. Through structural modification, it exhibits reduced binding to ApoE proteins and lowered liver affinity compared to traditional ionizable lipids. Instead, Lipid 10a-26 demonstrates strong splenic tropism—in non-human primate studies, it effectively delivers payloads to the spleen and immune cells in peripheral blood, such as T cells, NK cells, and macrophages, enabling the possibility of "in vivo CAR-T" therapy. Its pKa is tuned to approximately 6.0–6.5, allowing rapid protonation in the acidic endosomal environment, which promotes endosomal membrane disruption and efficient cytosolic release of circular RNA.

IC8 is an ionizable cationic lipid. It has been used in combination with other lipids for the formation of lipid nanoparticles (LNPs). Immunization with severe acute respiratory coronavirus 2 (SARS-CoV-2) spike glycoprotein mRNA in IC8- and manganese-containing LNPs induces IgG responses to SARS-CoV-2 Delta and Omicron variants in mice.1 Administration of mRNA encoding B7-H3 X CD3 bispecific T cell engaging (BiTE) antibodies in IC8-containing LNPs reduces tumor growth in MV4-11 and A375 mouse xenograft models.

80-O16B is a disulfide bond-containing ionizable cationic lipidoid. It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of CRISPR complementary single-guide RNA (sgRNA) and Cas9 for genome editing in mice. LNPs containing 80-O16B conjugated to phenylboronic acid (PBA) and encapsulating an mRNA reporter increase luciferase reporter expression in HeLa cancer cells.2 LNPs containing 80-O16B conjugated to PBA and encapsulating p53 mRNA decrease the viability of DU145 prostate and SiHa and HeLa cervical cancer cells.

ALC-0315 analogous-1 is a derivative of the ionizable cationic amino lipid ALC-0315. It has been used in the synthesis of ionizable cationic lipids used in the generation of lipid nanoparticles (LNPs).

TNT-b10 is a novel Lipid-like compound suitable for delivery of siRNA and mRNA both in vitro and in vivo TNT-b10 LLNs was more than 10-fold more potent than TNT-a10 LLNs formulated under the same condition.

YK-009 is an advanced, biodegradable ionizable lipid designed for efficient mRNA delivery. Via intramuscular injection, it demonstrates superior targeting to draining lymph nodes, boosting immune cell transfection for vaccines. When administered intravenously, it distributes to the liver but leverages a highly degradable chemical backbone to ensure rapid clearance post-endosomal escape. This effectively eliminates the risk of long-term tissue accumulation and liver toxicity seen in traditional lipids. Delivering a balance of high transfection efficiency and exceptional biocompatibility, YK-009 is an ideal component for safe and potent lipid nanoparticle (LNP) formulations.

Lipid 8 iLNPs were used to deliver CRISPR-Cas9 mRNA and sgRNA which targeted to the PLK1 gene. The safety and excellent intracerebral diffusion performance of lipid 8 iLNPs ensured that the survival of murine glioblastoma multiforme (GBM) mice was extended. The median survival was extended by approximately 50% and the overall survival was increased by 30%. The treatment of metastatic adenocarcinoma was executed by the EGFRtargeted lipid 8 iLNPs. These iLNPs possessed the ability of tumor targeting, which could increase the accumulation of CRISPR-Cas9 mRNA and sgRNA within the tumor cells. After a single intraperitoneal administration,
80% PLK1 gene was edited and the overall survival of mice with high-grade ovarian cancer malignant ascites was enhanced by
80% . These results demonstrate the clinical potential of CRISPR-Cas9 gene editing system can be delivered by iLNPs for treating tumors, and provide new ideas for tumor gene therapy.

SM-102 N-oxide is potential impurity in commercial preparations of SM-102.

ND-O1 (SM-86 Analog-2) is a novel ionizable lipid designed to improve the delivery of siRNA via lipid nanoparticles (LNPs) for treating liver fibrosis. It is derived from SM-86 (structurally similar to SM-102, used in COVID-19 mRNA vaccines) but incorporates an ether bond within its hydrophobic tail, a first-of-its-kind modification aimed at enhancing delivery efficiency. In Vitro Efficiency: ND-O1 LNPs (LNP-O1) showed significantly higher siRNA transfection efficiency in activated fibroblasts compared to Lipid 5 LNPs (LNP-M). In Vivo Efficacy: In a CCl4-induced liver fibrosis mouse model, LNP-O1/siHSP47 (loaded with HSP47-targeting siRNA) reduced HSP47 expression by ~84%, threefold more effective than LNP-M. This led to a dramatic reduction in collagen deposition and marked improvement in liver fibrosis. Safety: The ether bond modification did not introduce additional toxicity, maintaining biocompatibility. ND-O1 represents a breakthrough in ionizable lipid design, demonstrating that strategic placement of ether bonds in hydrophobic tails can enhance LNP performance without compromising safety. Its success highlights its potential for clinical translation in RNA-based therapies for liver fibrosis and other hepatic diseases.

DMHAPC-Chol is a cationic cholesterol. Liposomes containing DMHAPC-chol have been used for DNA plasmid delivery in vitro and in vivo in a B16-F10 mouse xenograft model. Liposomes containing DMHAPC-chol are cytotoxic to B16-F10 cells. DMHAPC-Chol, as part of a lipoplex with DOPE, has also been used to deliver DNA into mouse lung via intratracheal injection, resulting in a heterogeneous distribution in the bronchi and bronchioles, and to deliver VEGF siRNA into A431 and MDA-MB-231 cells, which secrete VEGF.

10-Nitrooleic acid (CXA-10), a nitro fatty acid, has potential effects in disease states in which oxidative stress, inflammation, fibrosis, and/or direct tissue toxicity play significant roles.

OF-02 (OF-2) is an alkenyl amino alcohol (AAA) ionizable lipid for highly potent in vivo mRNA delivery.Alkenyl amino alcohols (AAA) are a functional group found in sphingosine and other bioactive molecules. It was used to prepare AAA-based ionizable lipids through ring-opening reactions between alkenyl epoxides (AEs) and polyamine cores. These AAA-based iLNPs could promote high-level protein expression Therefore, AAA-based ionizable lipids OF-00, OF-01, OF-02, and OF-03 were prepared. The results of in vivo delivery of human erythropoietin (hEPO) mRNA showed that the AAA ionizable lipid OF-02 with the linoleic acid derivative could effectively deliver hEPO mRNA. Compared with the positive control CKK-E12, OF-02 showed an increased ability to induce serum EPO protein expression by nearly twofold (Figure 7b). Likewise, it outperformed two benchmark ionizable lipids (503013 and C12-200) in the nucleic acid delivery field. Furthermore, the mRNA delivered by OF-02 iLNPs was mainly in vivo.translated into the liver. The liver-targeting ability of OF-02 iLNPs improves their delivery efficiency. Therefore, the OF-02 iLNPs may become excellent delivery vehicles for the treatment of liver diseases without other side effects of damage to other organs during the treatment

DORI, N-(2-hydroxyethyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propan-1-aminium bromide, is an ionizable cationic lipid with lower cytotoxicity and high transfection efficiency. Reagent grade, for research use only.

CL15F 9-5, a piperidine-based ionizable lipid, exhibits favorable properties for mRNA delivery in lipid nanoparticles (LNPs). Its apparent pKa ranges between 6.24–7.15, ideal for mRNA encapsulation and endosomal escape. LNPs formulated with CL15F 9-5 (50:38.5:10:1.5 molar ratio of ionizable lipid:cholesterol:DSPC:DMG-PEG2k) demonstrated high mRNA encapsulation efficiency (>90%) and maintained physicochemical stability (size, PDI, zeta potential) during storage at 4°C for 5 months . In vitro, CL15F 9-5 LNPs showed superior luciferase expression in HEK-293T cells compared to CL4F-based LNPs. In vivo, liver-targeted LNPs delivered hEPO mRNA effectively, with sustained serum hEPO levels post-storage. Intravenous administration of FLuc mRNA-loaded CL15F 9-5 LNPs yielded strong hepatic bioluminescence, confirming liver tropism. As a vaccine candidate, CL15F 9-5 induced robust antigen-specific cellular immunity in mice, with a 14-fold increase in IFN-γ spots compared to SM-102. Its enhanced stability is attributed to reduced aldehyde impurities, minimizing mRNA-lipid adduct formation.

A2T2C9 (CP-LC-1465) is an imidazole-based ionizable lipid with branched hydrophobic chains and β-propionate linkers, formulated in four-component LNPs for spleen-targeted mRNA delivery. It achieves >80% spleen selectivity with protein expression exceeding 1×10⁷ p/s in mice, driven by its negative zeta potential (-9.7 to -19 mV). Structural features including imidazole polar head and branched acrylate (C9) enhance splenic tropism, potentially through distinct protein corona interactions. Demonstrated low cytotoxicity (>75% viability in splenic cells) and biodegradability via pH-sensitive linkers enable efficient mRNA delivery without permanent charged additives, outperforming conventional anionic SORT systems in selectivity and therapeutic potential.

4A3-SC7​​ is a proprietary, ionizable lipid component central to the SORT LNP platform developed for targeted organ delivery. It features a unique ​​branched-tail structure​​ designed to enhance mRNA encapsulation and endosomal escape. In the study, it served as the ​​primary ionizable lipid​​ in both Liver SORT LNPs and updated Lung SORT LNPs. For liver targeting, it was formulated at ​​15.04 mol%​​ alongside helper lipids (DOPE: 23.04%, Cholesterol: 38.72%), PEG-lipid (DMG-PEG2000: 3.2%), and the liver-targeting lipid ​​4A3-Cit (20 mol%)​​. This specific composition (Total lipid:RNA = 20:1 wt/wt) yielded LNPs with ​​~74 nm size​​, ​​low PDI (0.17)​​, and ​​high encapsulation efficiency (87%)​​ for large mRNAs like ABE editors (~5000 nt). Its branched-tail architecture was critical for stabilizing nanoparticles encapsulating large RNAs, overcoming a key limitation of previous formulations. 4A3-SC7-based Liver SORT LNPs enabled ​​>40% base editing in hepatocytes​​ in vivo, achieving durable correction of the disease-causing SERPINA1 mutation in PiZ mice and significantly reducing pathological protein aggregates. In the updated DualSORT system, 4A3-SC7 was also paired with ​​DORI​​ (instead of DOTAP) for improved lung targeting, demonstrating its versatility as a foundational ionizable lipid for multi-organ gene editing therapeutics.

306-N16B is a lipidnanoparticle, and allows systemic codelivery of Cas9 mRNA and sgRNA. 306-N16B can transport mRNA to the pulmonaryendothelial cell. 306-N16B can be used for research of genome editing-based therapies. Based on the same lipid libraries with 306-O12B, the researchers also found that N-series ionizable lipids were able to selectively deliver mRNA to the lungs of mice. Compared with the liver-targeted O-series ionizable lipids which contained ester bond in lipid tail found in previous work, such as 306-O12B, the N-series ionizable lipids with the lipid tail containing amide bond prefer to deliver mRNA to the lung. As a N-series ionizable lipid, the chemical structure of the 306-N16B is shown in Figure 4a,b. The difference of organ targeting may be due to their adsorption of different protein coronas during blood circulation caused by their different structures mentioned earlier.It has shown that the second major protein of the protein corona adsorbed by liver-targeting 306-O12B iLNPs was apolipoprotein E (ApoE), while the three dominant proteins in the protein corona adsorbed by lung-targeting 306-N16B iLNPs were serum albumin, fibrinogen beta chain, and fibrinogen gamma chain. However, the 306-N16B iLNPs showed less organ selectivity when systematically codelivered Cas9 mRNA and sgRNA in vivo, which could simultaneously activate tdTomato expression in the liver and lung of Ai14 mice, whereas single mRNA delivery could almost exclusively deliver mRNA to the lungs. This surprising phenomenon requires further investigation. Both the change of iLNPs charge and the change of lipids functional group can influence the distribution of iLNPs in vivo due to the altering of protein corona composition. Therefore, it is possible to control the organ targeting of iLNPs by controlling the composition of the outer protein corona of iLNPs.

Lipid 11-A-M (LNP Lipid-8) is a specialized single-tail, multi-head ionizable cationic lipid engineered for targeted nucleic acid delivery to T cells. Unlike traditional lipids that exhibit strong liver tropism, 11-A-M formulations successfully bypass hepatocytes, resulting in negligible liver accumulation and toxicity. Upon intravenous administration, it naturally localizes to peripheral immune organs, enabling robust gene silencing and transfection specifically within splenic CD3⁺ T cells, with a higher efficiency in CD8⁺ cytotoxic T cells over CD4⁺ helper T cells. This liver-evading, T cell-specific targeting profile makes it a premier tool for in vivo immunotherapy and in situ cell reprogramming.

Fluorescent SM-102 (NBD-SM-102) is a premium, dye-conjugated ionizable cationic lipid designed for advanced nanomedicine and mRNA delivery research. By covalently integrating a bright, green-fluorescent nitrobenzofurazan (NBD) probe into the industry-standard SM-102 skeleton, this high-purity reagent operates as an indispensable visual tracer. It empowers researchers to seamlessly track cellular uptake, monitor tissue biodistribution, and quantify endosomal escape efficiencies via fluorescence microscopy and flow cytometry. Crucially, this NBD-SM-102 derivative preserves the native ionizable property (\(pK_a \approx 6.68\)) and optimal membrane-fusion dynamics required for lipid nanoparticle (LNP) assembly and transfection, ensuring experimental formulations accurately mimic functional delivery vectors. This reliable reagent is ideal for accelerating lipid-mix optimization, high-throughput screening, and nucleic acid therapeutics development pipeline.

80-O18 is a lipidoid known for its exceptional ability to enhance overall cellular uptake, showcasing significant potential as an effective delivery agent.

Acuitas II-10 is an novel ionizable amine lipid used for mRNA delivery from Acuitas Therapeutics patent WO2016176330A1

L1 is a biodegradable, branched self-immolative lipid optimized for ​​high-efficiency mRNA delivery​​. Its disulfide-based architecture enables rapid glutathione-triggered degradation in the cytosol (liver half-life: 4.2 days), promoting rapid clearance while maintaining serum stability. In vivo, L1 achieves ​​exceptional mRNA translation​​, producing twice the hEPO protein levels of the clinically approved MC3 lipid at 0.1 mg/kg. Its reported apparent pKa is 6.57. Tolerability is dose-dependent: supplementary clinical observations record abnormalities at 5 mg/kg through 48 hours; these findings should be considered alongside body-weight and cytokine measurements. Structural features (C7 alkyl tails, carbamate linker) balance potency and biodegradability, making L1 ideal for mRNA vaccines and protein-replacement therapies.

S-Ac7-DOg​​ is an ​​ionizable lipid​​ engineered for optimized mRNA delivery to the retina, featuring a ​​sulfur-based ester bond​​ (S-Ac) and ​​dual oleyl glyceride chains​​ (DOg). Its pKa (~6.74) is finely tuned to enhance ​​endosomal escape​​ in acidic environments, enabling efficient cytosolic mRNA release. Unlike traditional lipids (e.g., C12-200, MC3), S-Ac7-DOg incorporates ​​biodegradable ester linkages​​ that hydrolyze intracellularly, minimizing lipid accumulation and reducing innate immune activation. In vitro, S-Ac7-DOg LNPs achieved >80% transfection efficiency in retinal cells (ARPE-19, MIO-M1) with ​​negligible cytokine secretion​​, outperforming MC3 and rivaling C12-200 while avoiding the latter’s high immunogenicity. In vivo, intravitreal delivery in mice showed ​​robust protein expression​​ in the optic nerve head (ONH) and Müller glia (75–100% of eyes), sustained for ≥7 days. Critically, it induced the ​​lowest immunogenicity​​ among tested lipids: minimal leukocyte infiltration (<1.5-fold vs. PBS), no microglial reactivity, and reduced GFAP upregulation.

CHCha-10 is an amino acid-derived ionizable lipid engineered for pulmonary gene therapy. Its optimal surface charge (-0.126 mV) enables efficient mucus penetration, while a pKa of ~7.0 facilitates endosomal escape. Its unique conical structure promotes membrane fusion and mRNA release. In animal models, CHCha-10-based LNPs achieved highly efficient and specific editing of lung epithelial cells, particularly stem-like basal cells (~44%), with effects persisting through tissue renewal. It also demonstrated excellent efficacy and safety in ferrets, a model closely mimicking human lung physiology.

Dlin-MeOH is a lipid product for use in drug delivery systems.

DOIC is a cationic lipid that can be used for RNA vaccines.

TS-202 is a novel ionizable lipid for RNA delivery.

304O13 is a novel Biodegradable lipidoid for RNA delivery.

Lipid 10 is a novel ionizable cationic lipid be used for delivery of therapeutic RNA to the Bone Marrow in Multiple Myeloma Using CD38-Targeted with Lipid 10-LNP.

E10i-494 is a branched ionizable lipid designed to enhance the delivery of mRNA and CRISPR-Cas9 ribonucleoprotein (RNP) complexes. It belongs to the Branched Endosomal Disruptor (BEND) lipid family, which features terminal branching to improve endosomal escape and cellular uptake.E10i-494 demonstrated exceptional performance in T cell engineering, achieving >80% transfection efficiency in primary human T cells. This is significantly higher than the ~70% efficiency achieved by the linear lipid C14-494.The isopropyl branch enhances the lipid's ability to penetrate and disrupt endosomal membranes, leading to improved release of mRNA and RNPs into the cytoplasm.Despite its high efficiency, E10i-494 exhibits low cytotoxicity, making it suitable for therapeutic applications.E10i-494 is particularly effective for delivering mRNA to T cells, making it a promising tool for CAR-T cell therapy and other immunotherapies.Its ability to deliver CRISPR-Cas9 RNPs efficiently also makes it suitable for in vivo gene editing applications.

MIC1 is a set of multi-charged lipids with four tertiary amino nitrogen atoms (4N4T) which could be constructed and applied to form novel lipid nanoparticles. 4N4T-LNPs based on MIC1 exhibit much higher mRNA translation efficiency than the approved SM-102-LNPs. 4N4T-LNPs are successfully applied to DS mRNA vaccine and the vaccines worked well against SARS-CoV-2 and its variants, including Delta and Omicron.

IAJD93(IAJD-93) is a pentaerythritol-based one-component ionizable amphiphilic Janus Dendrimer (IAJD), delivery systems for mRNA delivery.

GL6 is a trivalent GalNAc-lipid conjugate designed for ASGPR-mediated hepatic delivery. It features a lysine-based scaffold covalently linked to three GalNAc moieties via a ​36-unit PEG spacer, anchored by a ​1,2-O-dioctadecyl-sn-glyceryl (DSG) lipid tail. This structure balances ligand accessibility (via optimized PEG length) and nanoparticle stability (via hydrophobic DSG anchoring). Compared to GL3 (TRIS scaffold, same PEG length), GL6’s simplified lysine scaffold improves manufacturability. In LDLR-deficient models, GL6 enabled ​61% liver editing (vs. 5% with standard LNPs) at 2 mg/kg, demonstrating superior ASGPR targeting. Its design minimizes ligand crowding (0.05 mol% surface density) while maximizing endosomal escape and durable gene editing.

Lipid 20b​​ is a thiophene-based ionizable lipid synthesized via the Gewald reaction. It features dual unsaturated linoleic tails (C18:2) attached to the same side of the thiophene core and a tertiary amine headgroup. Formulated into LNPs (~100 nm, PDI ~0.2) with DSPC/cholesterol/DMG-PEG, it exhibits high mRNA encapsulation (>90%). Unlike traditional lipids, 20b lacks a pH-dependent ionization profile, likely due to electron delocalization in the thiophene ring. Intravenously, 20b LNPs transfect the liver and spleen in mice. Notably, subretinal delivery in mice and non-human primates (NHPs) achieved robust mRNA expression in photoreceptors (35% rods, 45% cones at high dose) and retinal pigment epithelium (RPE) with minimal acute toxicity. Immunosuppression enhanced rod transfection efficiency. High-dose administration in NHPs caused subretinal debris, but low doses (2.5 µg mRNA) maintained retinal health. This lipid demonstrates potential for liver and retinal gene therapy.

Lipid 29d is an ionizable lipid containing a thiophene moiety (Thio-lipid) for mRNA delivery. Lipid 29d enables LNPs to transfect the lung and spleen.

FO-32 is an artificial intelligence-guided designed ionizable lipid for RNA delivery to the muscle, lung and nose. FO-32 LNPs enable potent transfection throughout the whole ferret lung epithelium, from trachea to alveoli.

FO35 is an artificial intelligence-guided designed ionizable lipid for RNA delivery to the muscle, lung and nose. FO-35 LNPs enable potent transfection throughout the whole ferret lung epithelium, from trachea to alveoli.

18-2-9b2 is a dendron-like degradable ionizable lipid which facilitates mRNA delivery to splenic macrophages. 18-2-9b2 LNP encapsulating therapeutic BTB domain and CNC homologue 1 (BACH1) mRNA exhibited proficient BACH1 expression and subsequent Spic downregulation in splenic red pulp macrophages (RPM) in a Spic-GFP transgene model.

YK-TLR-001 is a cyclic acetal-based ionizable lipid for mRNA delivery. YK-TLR-001 LNPs are demonstrated to enhance mRNA expression in the spleens and to induce exceptional maturation of antigen-presenting cells (APCs) and to promote antigen presentation.

2Ac3-C18 is a core-degradable ionizable lipid with two ester-linked branches, two tertiary amines and two C18 alkyl tails. Its four-component LNPs, formulated with DOPE, cholesterol and DMG-PEG2000, showed spleen-selective reporter-mRNA expression after intravenous administration in mice.

AP60 is a novel, biomimetic ionizable lipid, identified as the lead compound from a library of 67 aminophosphonate-derived lipids. Inspired by the structure of natural phospholipids, it forms the core component of lipid nanoparticles within the CROSS delivery platform. AP60-based LNPs demonstrate superior efficiency in delivering mRNA and circular RNA to neuronal cells and astrocytes compared to the clinically used MC3 LNP. In a mouse model of spinal cord injury, AP60 LNPs achieved significantly higher protein expression at the lesion site (13.7-fold locally, 4.6-fold intravenously) while concurrently reducing off-target accumulation in the liver by nearly 5-fold. This indicates improved targeting to the central nervous system injury site and a potentially better safety profile. Its cellular uptake is primarily mediated by clathrin-mediated endocytosis and macropinocytosis, followed by efficient endosomal escape. By encapsulating therapeutic circular RNAs encoding Sox2, Ascl1, and GDNF, AP60 LNPs enable effective in vivo reprogramming and neuroprotection, leading to significant functional recovery of bladder and locomotor functions after spinal cord injury.

Lipid 2298 is a novel ionizable lipid developed by Sai Biomedicine demonstrates excellent performance with a spleen-to-liver ratio of 3.448​ and a very high total expression level of 2.4E+07. Lipid 2298 offers a strong balance of efficient systemic protein production and clear preferential delivery to the spleen.

D-2 is a novel, custom-synthesized ionizable cationic lipid that serves as the core functional component of the targeted lipid nanoparticle (LNP) delivery system. Its key function is to enable the efficient in vivo delivery of therapeutic mRNAs. Under acidic conditions, it ionizes to a positive charge, allowing it to complex with and encapsulate the negatively charged mRNAs encoding the anti-FAP CAR and Lgmn protease. At physiological pH, it returns to a neutral state, which helps reduce systemic toxicity and is crucial for promoting the release of the mRNA payload inside the target macrophages within the infarcted heart. As part of the optimized LNP formulation, D-2 is fundamental for achieving high transfection efficiency, thereby enabling the in situ generation of efferocytosis-boosted CAR-Ms to treat cardiac fibrosis.

6A1‑SC8 is a biodegradable ionizable lipid developed for LNP-based nucleic acid delivery. With multi-tertiary amine core enabling optimal endosomal escape and built-in hydrolyzable ester linkages for in vivo metabolic clearance, it efficiently encapsulates mRNA, sgRNA and gene-editing payloads. When blended with helper lipids or modified via the SORT strategy with cationic additives like DOTAP, it generates organ-targeted LNPs ranging from liver to cardiac tropism, widely applied in preclinical gene therapy, in vivo CAR‑T and rare disease therapeutic research.

113-AA-C8C14 is a spleen-tropic ionizable lipid with inherent splenic organ selectivity. Its formulated LNPs drastically reduce off-target liver uptake and drive 57-fold higher mRNA expression in spleen versus benchmark LNPs. It preferentially delivers nucleic acids to splenic immune cells like macrophages and T lymphocytes, supporting in vivo CAR-T engineering and mRNA vaccine research with minimal accumulation in other visceral organs.

Lipid 51 is a top-performing thioglycerol-based biodegradable ionizable lipid disclosed in PCT patent WO2026/147683 (Eli Lilly, filed Dec 16, 2025). Built with cleavable thioester linkages, it balances neutral surface charge at physiological pH and protonatable amines in acidic endosomes for efficient mRNA encapsulation and endosomal escape. Formulated into LNPs with DSPC, cholesterol and DMG-PEG2K, it exhibits favorable particle size, low PDI and high RNA loading efficiency. In intracerebroventricular (ICV) mouse tests targeting central nervous system (CNS), it delivers Cre mRNA to brain neurons far more potently than Lipid 1/2/3, with the highest tissue fluorescent signal among all tested candidates. It shows low cellular toxicity in vitro and robust CNS tropism, making it an optimal carrier for brain-targeted mRNA and CRISPR gene editing therapeutics.

FL0445 is a biodegradable, multi-branched ionizable lipid featuring an ionizable amine-containing headgroup together with ester and carbonate linkages. When formulated with DOPE, cholesterol, and a PEG lipid, FL0445-LNP enabled efficient delivery of both linear mRNA and structurally constrained capped circular RNA (Cap-cirRNA). In the reported study, the optimized formulation produced substantially higher in vitro protein expression than benchmark LNPs based on MC3, SM-102, or ALC-0315 and demonstrated functional nucleic-acid delivery following intravenous, intramuscular, and subcutaneous administration in mice. The platform was also evaluated for mRNA vaccination, ASO-mediated gene silencing, pDNA delivery, and GLP-1-encoding Cap-cirRNA. FL0445-LNP induced comparatively low inflammatory cytokine responses and showed favorable single-dose tolerability in the tested mouse models, supporting its further evaluation as a versatile preclinical delivery lipid for mRNA, circular RNA, and other nucleic-acid modalities.

TTP-3 is an asymmetric Ugi-derived ionizable lipid developed specifically for pulmonary delivery of structured suppressor tRNA cargo. Its architecture combines a dimethylaminopropyl ionizable headgroup, two amide-containing linkages, and chemically distinct hydrophobic tails. Selected from a 1,000-member lipid library, TTP-3 showed the strongest suppressor-tRNA delivery in a cystic-fibrosis-relevant air–liquid interface model containing artificial mucus. An optimized formulation containing TTP-3, DOPE, β-sitosterol, and C14-PEG2000 produced approximately 38-fold higher functional pulmonary reporter expression than MC3 following intratracheal administration in mice. TTP-3 LNPs preferentially delivered tRNA to airway epithelial cells, including ciliated, club, ionocyte, and basal progenitor populations. When combined with chemically modified suppressor tRNAs, the platform restored CFTR expression and function in cellular, mouse, and patient-derived organoid models. TTP-3 remains a preclinical research lipid, and further optimization is required for aerosol delivery, repeat dosing, and clinical translation.

C12-2aN is a crosslinked ionizable lipid developed for mRNA vaccine delivery and dendritic-cell metabolic reprogramming. Its structure combines two piperazine-based ionizable amine cores, a bis-amidine crosslinker, and four hydroxylated C12 hydrophobic tails. When formulated with DOPE, cholesterol, and C14-PEG2000, C12-2aN LNPs enhanced mRNA endosomal escape and activated AMPK–mTORC2-dependent glycolysis, supporting dendritic-cell maturation and antigen presentation. In preclinical mouse studies, C12-2aN LNPs generated robust humoral and cellular immune responses in SARS-CoV-2 RBD and OVA cancer-vaccine models. The formulation also demonstrated reduced liver-associated off-target expression and lower acute inflammatory markers than the tested control formulations. C12-2aN is a preclinical research lipid intended for evaluating metabolically active mRNA vaccine delivery systems.

ST12 is a lipid-conjugated DMXAA prodrug designed for temporally controlled STING activation in mRNA vaccine formulations. Its structure integrates a mouse-specific STING agonist, a biodegradable ester linker, an RNA-interacting tertiary amine domain, and two hydrophobic tails. When incorporated as a partial replacement for SM-102, ST12 preserves early antigen mRNA translation and subsequently releases DMXAA to activate STING. This delayed activation supports localized type I interferon signaling, enhanced antigen-specific CD8-positive T-cell responses, and improved antitumor immunity. In preclinical OVA and HPV tumor models, ST12-based Syn-STING vaccines suppressed tumor growth and prolonged survival. ST12 remains a preclinical research lipid developed specifically around DMXAA-sensitive STING systems.

Lipid C3 is an ionizable cationic lipid (pKa = 5.05-5.671).1,2 It has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA in vitro and in vivo.

CP-LC-1254 is listed as a ionizable lipid for laboratory research use.

Lipid N2-3L is listed as a ionizable lipid for laboratory research use.

80-O14B is listed as a ionizable lipid for laboratory research use.

PNI 132, an ionizable lipid derived from the patent WO2020252589A developed by Precision Nanosystem, is useful in the formulation of lipid nanoparticles.

VC1052 is the component of Vaxfectin. Vaxfectin is a cationic lipid-based adjuvant that can be used for plasmid DNA- and protein-based vaccines.

C10-200-based LNPs show enhanced liver tropism for mRNA delivery, outperforming branched-chain lipidoids (e.g., C12-200) in hepatic reporter gene expression. The system's therapeutic potential is confirmed through successful EPO production, with measurable increases in circulating protein levels following administration.

IM21.7c is listed as a ionizable lipid for laboratory research use.

BNT-51 is an ionizable thiolipid developed by Biontech, characterized by its sulfur-containing moieties and a multiarm dendron-like architecture. Synthesized via reactions between amine-containing compounds and sulfur-based halides or sulfonates, it forms stable lipid nanoparticles (LNPs) optimized for mRNA delivery. The LNPs exhibit uniform particle size (80–100 nm, PDI <0.2), near-neutral zeta potential, and high mRNA encapsulation efficiency (>90%), while maintaining payload integrity through freeze-thaw cycles and extended storage. In vitro, BNT-51 demonstrates low cytotoxicity (>80% cell viability in C2C12, HepG2, and HEK293 cells) and superior transfection efficiency compared to conventional lipids, particularly in immune cells such as CD4+/CD8+ T cells within PBMCs. Its modular design allows integration of stealth lipids (e.g., PEG or vitamin E derivatives) to prolong circulation time and minimize immune activation, as evidenced by low hemolysis and complement activation risks. In vivo, BNT-51-based LNPs enable targeted mRNA delivery to splenic macrophages, achieving potent genome editing (e.g., Cre mRNA) and therapeutic protein expression (e.g., BACH1) in preclinical models. With its tunable structure, robust stability, and cell-specific tropism, BNT-51 holds promise for advancing mRNA therapeutics in gene editing, cancer immunotherapy, and regenerative medicine, offering a versatile platform for next-generation nanomedicine.

ATX-054 which is from Arcturus RNA delivery platform, is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA.

Lipid 5D8 is a novel biodegradable ionizable lipid (IL) developed through a combinatorial chemistry strategy to overcome the limitations of conventional lipid nanoparticles (LNPs) in mRNA delivery. Synthesized via a one-step, solvent-free Michael addition reaction between amine and thiol monomers, 5D8 features asymmetric lipid tails and a biodegradable ester backbone, ensuring both structural versatility and reduced toxicity. In preclinical studies, 5D8-based LNPs demonstrated exceptional liver-targeting efficiency and mRNA delivery performance. A single intravenous dose (1 mg/kg) achieved 61% CRISPR-Cas9-mediated editing of the TTR gene in mice, reducing serum TTR protein by 90%, outperforming benchmark lipids like C12-200 (51% editing). Moreover, 5D8 enabled efficient delivery of base editors (ABE8.8 and CBE4max), achieving 42% PCSK9 editing (74% serum protein reduction) and correcting hereditary tyrosinemia in mice, significantly extending survival. Beyond gene editing, 5D8 LNPs effectively delivered siRNA (complete serum TTR clearance at 0.05 mg/kg) and enhanced hepatocyte targeting by enriching apolipoprotein E on particle surfaces. Crucially, 5D8 exhibited superior biocompatibility with no hepatotoxicity (normal ALT/AST levels), contrasting traditional LNPs. Its rapid biodegradability and "plug-and-play" design make 5D8 a versatile platform for mRNA therapeutics, holding broad potential for treating genetic disorders, cardiovascular diseases, and beyond. This innovation represents a critical advancement toward safer, high-efficiency clinical translation of gene-editing therapies.L

Galnac Lipid 29 is listed as a galnac lipids for laboratory research use.

Galnac Lipid 83 is developed by Prime Medicine Patent: WO2024220807.Galnac Lipid 83 83 is a GalNAc-conjugated lipid designed for targeted liver delivery. It features a triantennary GalNAc ligand linked via a PEG spacer (e.g., -(CH2CH2O)n-) to a branched hydrophobic tail (C18 alkyl chains). The structure includes amide/ester bonds for stability and a stereospecific configuration (R/S) to optimize ASGPR receptor binding. Integrated into lipid nanoparticles (LNPs), it enhances hepatic uptake of nucleic acids (e.g., mRNA, gene editors) by leveraging ASGPR-mediated endocytosis. Its design balances hydrophilicity (PEG) and lipophilicity (alkyl chains) for efficient encapsulation and in vivo delivery, supporting therapeutic applications in liver-specific gene editing or RNA therapies.

GalNAc Lipid 1002 is a trivalent GalNAc-lipid conjugate designed for ASGPR-mediated hepatic delivery. It features a lysine-based scaffold covalently linked to three GalNAc moieties via a ​12-unit PEG spacer, anchored by a ​1,2-O-dioctadecyl-sn-glyceryl (DSG) lipid tail.

GalNAc Lipid 1005 is a trivalent GalNAc-lipid conjugate designed for ASGPR-mediated hepatic delivery. It features a lysine-based scaffold covalently linked to three GalNAc moieties via a ​44-unit PEG spacer, anchored by a ​1,2-O-dioctadecyl-sn-glyceryl (DSG) lipid tail.

Lipid 1 HG3 serves as a key component in LNPs specifically engineered for in vivo delivery of closed-end DNA (ceDNA), demonstrating efficient nucleic acid encapsulation and targeted release capabilities.

DMT7 (pKa 6.5) is an ionizable cationic lipid engineered for co-delivery of mRNA and immunomodulators via LNPs. In 4T1 breast cancer metastasis models, DMT7 LNPs carrying IL-12 mRNA and STING agonist MSA-2 significantly reduce tumor burden and pulmonary metastases while modulating T cell populations. The formulation demonstrates broad immunotherapeutic effects in melanoma models, shifting tumor macrophages toward the M1 phenotype, reducing Tregs, and elevating pro-inflammatory cytokines (IL-12, IL-2, TNF-α, IFN-γ).

7-1 lipid represents a novel ionizable cationic compound designed for nucleic acid delivery applications.

G0-C14 analog is a derivative of the ionizable cationic lipid G0-C14.

Lipid 17 is a novel, highly potent ionizable lipid designed for mRNA delivery within lipid nanoparticles (LNPs) developed by AstraZeneca . Its structure features a secondary amine head group attached to a cyclic ether moiety (specifically, the 2-oxaspiro[3.3]heptan-6-amine head group). It possesses an asymmetric tail architecture: one tail is derived from heptadecan-9-ol (a branched C17 secondary alcohol), while the other tail is a modified nonyl chain (C9) with a key ethyl branch at the 3-position. The linker connecting the head group to the tails has a length equivalent to n=3 (three methylene units) as defined in the study. This specific combination of the secondary amine cyclic ether head group, asymmetric tails, and the ethyl branch at the 3-position of the nonyl chain proved critical for its exceptional performance. When formulated into LNPs and administered intravenously in mice, Lipid 17 demonstrated a remarkable 6-fold increase in functional protein (eGFP) expression in the liver compared to the benchmark lipid MC3, with high statistical significance (P < 0.0001). This makes Lipid 17 one of the most active lipids identified in the study and a promising candidate for liver-targeted mRNA therapeutics.​​

Moderna Lipid II-6 is listed as a ionizable lipid for laboratory research use.

Lipid 19 is an engineered cationic lipid designed to optimize the delivery of RNA within lipid nanoparticles (LNPs) developed by Nitto. Its unique structure—featuring a dual-hydroxyl headgroup and tailored hydrophobic chains—enables highly efficient encapsulation of these fragile genetic payloads, protecting them from degradation. The resulting LNPs exhibit exceptional stability (<100 nm size), target the liver specifically for enhanced therapeutic impact, and support applications ranging from mRNA vaccines to gene-silencing therapies. This makes lipid 19 a pivotal advancement in precision nanomedicine for liver-related disorders.​

L649 is a next-generation, lung-targeting ionizable lipid specifically designed for systemic mRNA delivery developed by Hopewell. Belonging to the novel "N-series" lipid class, it features a unique structure with an amine-containing head group and hydrophobic tails incorporating amide bonds. This design enables L649 to form highly stable lipid nanoparticles (LNPs) that exhibit exceptional tropism for the lower respiratory tract (lungs, bronchi, trachea) following intravenous administration. It demonstrates superior efficiency in delivering therapeutic payloads (like mRNA) specifically to key lung cell types, including alveolar epithelial cells (AT1 and AT2) and bronchial cells, while minimizing off-target accumulation in organs like the liver. L649-based LNPs, particularly when formulated with helper lipids like POPE, combine high potency with significantly improved tolerability, allowing for effective dosing in vivo. This makes L649 a promising candidate for developing treatments for various lung diseases such as pulmonary fibrosis, COPD, lung cancer, and infectious diseases like COVID-19.​

HY-501​​ is a next-generation cationically ionizable lipid engineered for high-efficiency RNA delivery developed by Biontech. Formulated at ​​40–50 mol%​​ in lipid nanoparticles (LNPs) alongside DSPC, cholesterol, and polysarcosine-conjugated lipid ​​C14pSar23​​, HY-501 yields uniform, stable particles (80–100 nm) with >90% RNA encapsulation. It demonstrates ​​superior in vivo performance​​: driving 2-fold higher protein expression than benchmark lipids (EA-405/HY-405) in muscle tissue, minimizing off-target liver accumulation, and reducing immunogenic risks (near-zero complement activation and <5% hemolysis). Preclinically, HY-501-based LNPs encoding SARS-CoV-2 spike protein elicit potent neutralizing antibodies and T-cell responses, underscoring its utility in precision vaccines. Its combination of scalable synthesis, exceptional transfection efficiency, and biosafety establishes HY-501 as a transformative vector for therapeutic RNA delivery.

​​C-a16​​ is an ionizable lipid engineered through Mannich reaction chemistry, designed to revolutionize mRNA delivery by synergizing high efficiency with minimized immune activation. Synthesized by reacting a phenolic tail derivative, formaldehyde, and a branched tertiary amine core under optimized ethanol conditions, this lipid integrates antioxidant phenol groups directly into its structure. These phenol moieties serve as intrinsic radical scavengers, effectively neutralizing intracellular reactive oxygen species that typically degrade mRNA and trigger inflammation.In lipid nanoparticle formulations, C-a16 constitutes the functional backbone, enabling superior mRNA encapsulation efficiency while maintaining a stable nanoparticle size of approximately 80–100 nm. Critically, it outperforms conventional lipids like DLin-MC3-DMA by achieving significantly higher target-protein expression in vivo alongside markedly reduced pro-inflammatory cytokine secretion. The antioxidant capability is not incidental but fundamental—quenching the phenol groups drastically diminishes both ROS suppression and delivery efficacy, confirming the design's mechanistic elegance.C-a16 represents a paradigm shift: its biomimetic antioxidant architecture addresses the chronic trade-off between delivery potency and immunogenicity, unlocking safer therapeutic applications for vaccines and gene therapies.

TS41 is a trisulfide-derived ionizable lipid engineered for lipid nanoparticles (LNPs) to deliver mRNA therapeutics against multidrug-resistant bacterial pneumonia. Its optimized formulation, TS41S LNP, combines TS41 with helper lipids (e.g., DOPE, cholesterol) at a precise ratio, achieving a hydrodynamic diameter of ~105 nm, low polydispersity, and high mRNA encapsulation efficiency (~84%). This design enables efficient pulmonary delivery via intratracheal administration, with luminescence signals in lungs 4.8-fold higher than clinical benchmarks like SM-102 LNPs, ensuring targeted expression in epithelial cells, macrophages, and neutrophils. Crucially, TS41 LNPs exhibit potent anti-inflammatory properties by scavenging reactive oxygen species (ROS), reducing neutrophil infiltration and proinflammatory cytokines (e.g., IL-6, TNF-α) in infected lungs. In preclinical models, TS41S LNP encoding PB9 peptibody mRNA eradicated pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, improved survival rates to 80%, and minimized tissue damage without systemic toxicity. Its ROS-scavenging capability synergizes with antibacterial effects, offering a promising, translatable platform for combating resistant infections while controlling inflammation. Future enhancements, such as codon optimization or inhalation delivery, could further broaden its therapeutic potential.

4A2-B8-PH is an optimally designed thioketal-incorporated biodegradable ionizable lipid (TBIL) for mRNA delivery to pancreatic ductal epithelial cells. It features a 4A2 headgroup with three tertiary amines, a biodegradable thioketal-based B8 linker, and a branched PH tail. The thioketal linker enables ROS-responsive degradation in the tumor microenvironment, enhancing endosomal escape and mRNA release. In vivo, 4A2-B8-PH LNPs achieve 98.3% pancreas-specific targeting after intraperitoneal administration, with a 218-fold improvement in delivery efficiency compared to previous benchmarks. It successfully transfects 30.5% of pancreatic ductal epithelial cells and induces complete tumor regression in orthotopic PDAC models via IL-12 mRNA therapy, demonstrating high efficacy and safety.

Lipid 48​ is a leading ionizable lipid designed for therapeutic nucleic acid delivery. Its key function is to form the core of lipid nanoparticles (LNPs) that efficiently encapsulate and deliver cargoes like mRNA and CRISPR guide RNAs into cells. Its optimized structure allows it to remain neutral in the bloodstream for low toxicity but become positively charged in acidic cellular compartments (endosomes), where it disrupts the membrane to release the therapeutic payload. Data from the patent demonstrates its superior profile: it achieves high gene editing efficiency (e.g., ~80% indel rates in vitro and 16.2% in vivo in mouse liver) while maintaining low cytotoxicity (cell viability >80% at effective doses), establishing it as an ideal candidate for gene therapy applications due to its exceptional balance of potency and safety.

6F Lipid is a Fluorinated Ionizable Lipid breakthrough in mitochondria-targeted gene delivery

Lipid 5 is an ionizable lipid based on a macrocyclic cyclam headgroup. Its structure incorporates a benzylmethyl carbonate (BMC) linker, which contains an aromatic benzene ring, and a saturated C18 hydrophobic tail. Lipid 5 was mixed with helper lipids at a fixed molar ratio and formulated into mRNA-loaded lipid nanoparticles (LNPs) using microfluidic technology. Characterization data show that these LNPs have a hydrodynamic diameter of approximately 50-80 nanometers and a polydispersity index (PDI) below 0.2, indicating a small particle size with a uniform distribution. Their zeta potential at physiological pH is near neutral (ranging from -3 to +3 mV). The mRNA encapsulation efficiency, as determined by the Ribogreen assay, exceeds 95%. Cryo-transmission electron microscopy images reveal that the LNPs exhibit a typical spherical bilayer structure. In in vitro experiments, Lipid 5 LNPs mediated a higher level of luciferase protein expression in HEK293FT cells compared to the benchmark lipid DLin-MC3-DMA. In Balb/c mice, intravenous injection of LNPs encapsulating luciferase mRNA resulted in in vivo imaging signals predominantly concentrated in the lungs. Quantitative analysis indicated that the signal intensity in the lungs was over 100 times greater than that in the liver, with more than 95% of the total signal distributed in the lungs. In Ai9 reporter gene mice, two intravenous injections of Lipid 5 LNPs encapsulating Cre mRNA led to quantitative analysis of lung tissue sections showing that approximately 30% of lung cells were positive for tdTomato signal.

KC3-OA, chemically known as 3-((S)-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine, is an ionizable cationic lipid (ICL) optimized for lipid nanoparticle (LNP) formulations in nucleic acid delivery, particularly for mRNA vaccines. It features a unique structure with mono-unsaturated alkyl chains (C18:1), which enhances oxidative stability compared to polyunsaturated analogs like KC3, while maintaining efficient membrane fusion and endosomal escape capabilities. In LNP compositions, KC3-OA is typically incorporated at 46–54 mol% of total lipids, with an N/P ratio of 4–6 relative to mRNA, ensuring high encapsulation efficiency and transfection potency. Experimental data demonstrate that KC3-OA-based LNPs achieve superior mRNA expression in human dendritic cells, outperforming alternatives like KC3-PA or KC3-01 in both in vitro and in vivo models. For instance, in FIG. 2, KC3-OA LNPs showed ~2-fold higher mCherry expression at low mRNA doses (0.1 μg/mL) due to improved cellular uptake and reduced degradation. Its synergy with anionic phospholipids like DPPS (5 mol%) further enhances dendritic cell targeting via receptor-mediated internalization, leading to robust CD4+ and CD8+ T-cell responses against Mycobacterium tuberculosis antigens. This balance of stability, efficiency, and immunogenicity makes KC3-OA a leading candidate for next-generation vaccines.

Diamino lipid DAL4 is diamino lipid for the preparation of lipid nanoparticles (LNPs) encapsulated with mRNAs encoding cytokines including IL-12, IL-27 and GM-CSF. Diamino lipid DAL4 delivers mRNA to tumor cells to exert anti-tumor activity.

L31 is identified as a novel, proprietary ionizable cationic lipid that serves as the critical functional component within lipid nanoparticles (LNPs) engineered for CRISPR/Cas9 genome editing in head and neck squamous cell carcinoma (HNSCC). It was selected from a screened library of lipids for its superior performance. LNPs formulated with L31 exhibited excellent physicochemical properties, including a uniform size of 80-100 nm, low polydispersity, and high encapsulation efficiency (>85%) for both Cas9 mRNA and sgRNA. In vitro, L31-based LNPs demonstrated outstanding therapeutic efficacy, achieving approximately 68% gene editing of the oncogene SOX2 and an 88% reduction in cancer cell viability.For in vivo applications, L31-LNPs were further functionalized with anti-EGFR antibodies using the ASSET linker strategy to create targeted nanoparticles (tLNPs). This modification enhanced specific uptake by tumor cells. In a xenograft mouse model, intratumoral injection of these targeted L31-cLNPs co-encapsulating Cas9 mRNA and sgSOX2 led to potent tumor growth inhibition (90%) and a significant increase in survival, with tumor disappearance observed in half of the treated mice. In conclusion, L31 is a highly efficient ionizable lipid that forms the foundation of a potent targeted LNP platform for precise CRISPR-based cancer therapy against solid tumors.

Cl-4A3-LNSC8​ represents a novel class of thiourea-functionalized ionizable lipids engineered for selective organ-targeted mRNA delivery. Its core innovation lies in an anion-coordination strategy, where the parent lipid, 4A3-LNSC8, binds chloride ions (Cl⁻) via hydrogen-bonding interactions with its thiourea groups. This binding event is not merely structural but functionally critical, as it induces a significant shift in the surface pKa of the resulting lipid nanoparticles (LNPs) from approximately 5.54 to 8.79. This pKa modulation is the key mechanism that redirects the organotropism of the LNPs upon systemic administration. While the unmodified 4A3-LNSC8 LNPs preferentially deliver mRNA to the liver, Cl-4A3-LNSC8 LNPs effectivelyreprogram this tropism, enabling highly efficient mRNA delivery to secondary lymphoid organs (SLOs), particularly the spleen and lymph nodes. This platform demonstrates remarkable efficacy, achieving up to 65.7% gene editing efficiency in splenic macrophages in vivo, significantly outperforming benchmark delivery systems. Furthermore, by leveraging the coordination with different halides, such as iodine for computed tomography (CT) contrast, the system can be adapted for dual-modal theranostic applications, enabling simultaneous lymphatic metastasis imaging and therapeutic mRNA delivery.

4A3-LNSC8​ is a strategically designed thiourea-functionalized ionizable lipid that serves as the foundational core for a novel anion-coordination delivery platform. Its structure features a central 4A3 amine headgroup symmetrically extended with four hydrophobic tails, each incorporating a biodegradable ester linkage and a key thiourea-bridged linker. The inclusion of the thiourea group is the pivotal innovation, as it provides specific hydrogen-bonding sites capable of interacting with various halide anions (F⁻, Cl⁻, I⁻). When formulated into lipid nanoparticles (LNPs) without anion coordination, 4A3-LNSC8 itself exhibits a characteristic liver tropism, efficiently delivering mRNA to hepatocytes following systemic administration, with a measured surface pKa of approximately 5.54. However, its primary significance lies in its role as a versatile precursor. The strong anion-binding capability of its thiourea linkers allows for predictable modulation of the LNP's properties. Upon binding with anions like Cl⁻, the resulting complex (e.g., Cl-4A3-LNSC8) undergoes a significant pKa shift, which reprograms the LNP's in vivo fate, redirecting mRNA delivery from the liver to secondary lymphoid organs such as the spleen and lymph nodes. Thus, 4A3-LNSC8 is not merely an efficient ionizable lipid but a programmable scaffold that enables precise control over organ-targeting specificity through simple anion coordination, offering a powerful rational design strategy for advanced mRNA therapeutics.

244-9-cis is a novel ionizable lipid disclosed in United States Patent US 2026/0014075 A1, specifically engineered for advanced lipid nanoparticle (LNP) delivery systems. Its distinctive molecular architecture features biodegradable ester bonds, which contribute to excellent physicochemical properties such as a near-neutral surface charge (approximately -3 mV) for improved biocompatibility, an optimal pKa of about 6.2 to facilitate endosomal escape, and consistently high nucleic acid encapsulation efficiency exceeding 90%. In vivo studies confirm significantly enhanced delivery to hepatocytes and markedly higher therapeutic protein expression compared to control formulations, positioning 244-9-cis as a promising candidate for next-generation genetic medicines.

Compound 22, as detailed in United States Patent US 2026/0014089 A1, is a bifunctional ionizable lipid engineered for precision drug delivery. Its structure integrates a monosaccharide targeting headgroup, designed to bind specifically to DC-SIGN receptors on dendritic cells, via a sophisticated linker connected to a biodegradable lipid anchor. This design enables it to serve as a key component of lipid nanoparticles (LNPs), forming a targeted delivery system. By leveraging the specific carbohydrate-receptor interaction, these LNPs are preferentially internalized by dendritic cells, critical for initiating adaptive immune responses. In vivo studies from the patent, such as the biodistribution data shown in Figure 5, confirm effective accumulation in lymphoid tissues like the spleen and lymph nodes. Consequently, this targeted delivery enhances the potency of encapsulated payloads (e.g., mRNA vaccines) by ensuring professional antigen presentation, eliciting a stronger and more specific immune response—evidenced by higher neutralizing antibody titers—making it a powerful tool for next-generation vaccines and therapeutics.

Lipid OC7, as described in the patent WO2022207938A1, is a novel ionizable lipid that serves as the core functional component of the saNppa-LNP delivery system. Its key innovation lies in its unique biodegradable structure featuring an internal ester bond. Under typical physiological conditions, this bond hydrolyzes, triggering a charge shift from a cationic form that complexes nucleic acids to a zwitterionic form that releases them. This property is central to its role in enabling long-acting self-amplifying RNA (saRNA) therapies. Specifically, OC7 facilitates immune stealth by mitigating early interferon responses, supports sustained and efficient intracellular replication of saRNA even at low doses, and enables therapeutic protein expression that persists for over 28 days from a single administration. This combination of efficient delivery, controlled release, and extended duration of action makes OC7-based LNPs a promising platform for long-term treatments, such as for myocardial infarction, as demonstrated in the referenced research.

A1F5C5 is a core fluorinated ionizable lipid that forms the basis of the F5-LNP platform. Its key biological functions are multifaceted. Primarily, it enables efficient, targeted mRNA delivery in vivo. Following intravenous administration, F5-LNPs exhibit a strong tropism for the spleen and tumor sites, successfully transfecting over 70% of splenic macrophages and more than 20% of tumor-infiltrating macrophages. This allows for in situ cell engineering. Beyond delivery, A1F5C5 possesses intrinsic immunostimulatory activity. It promotes the maturation and activation of antigen-presenting cells (e.g., upregulating CD80/86 on dendritic cells) and enriches immune-related pathways like "cytokine-cytokine receptor interaction." Mechanistically, its unique 5-fluorine (F5) configuration confers superior membrane fusion capability, which is critical for efficient endosomal escape and cytosolic mRNA release. Therapeutically, when loaded with CAR mRNA, it serves as a platform for in vivo generation of CAR-macrophages (CAR-M). These CAR-M cells phagocytose tumors, reprogram the tumor microenvironment by shifting macrophages to an M1 phenotype, and activate CD8+ T cells. Notably, this approach synergizes powerfully with anti-PD-L1 therapy, achieving complete tumor regression in preclinical models.

C6mPhE-383 is a top-performing ionizable lipid featuring an aromatic ring and a bioreducible disulfide bond. Formulated into lipid nanoparticles, it preferentially delivers mRNA to lymphoid tissues (lymph nodes/spleen) while minimizing off-target liver accumulation after intramuscular injection. In a SARS-CoV-2 vaccine study, it elicited strong antibody responses, promoted protective effector memory T cells, and exhibited enhanced safety by significantly reducing systemic inflammatory cytokines compared to the standard SM-102 LNP.

A1T2C3 （CP-LC-1067） is a highly potent ionizable lipid designed for lung-targeted mRNA delivery. When formulated into lipid nanoparticles (LNPs), it produces particles approximately 80 nm in size with excellent uniformity and a high mRNA encapsulation efficiency (>94%). Its most distinguished feature is its exceptional organ selectivity. Following intravenous administration in mice, A1T2C3-based LNPs demonstrated a remarkable accumulation of over 94% of the signal in the lungs, with minimal distribution to other major organs. This makes it a leading candidate for developing therapeutics specifically targeted to pulmonary tissues.

GA-16 is a novel ionizable lipid designed with an N-(2-Hydroxyethyl)piperazine-N'-(4-butanesulfonic acid) (HEPBS) core. Its key functional characteristic is enabling highly efficient, liver-tropic mRNA delivery through an ApoE-mediated yet Low-Density Lipoprotein Receptor (LDLR)-independent cellular uptake mechanism. When formulated in LNPs with the helper lipid DEPE, GA-16 achieves superior protein expression. More importantly, this uptake pathway bypasses the canonical LDLR dependency, making it a strategically valuable component for developing therapies targeting genetic liver diseases like familial hypercholesterolemia, where patients often have deficient LDLR function.

K9 is a novel ionizable lipid designed by the multi-objective AI model MOLEA. Its core function is to enable tissue-selective mRNA delivery. When formulated into Lipid Nanoparticles (LNPs), K9 can preferentially deliver mRNA efficiently to articular chondrocytes while significantly reducing delivery to hepatocytes. This facilitates targeted drug delivery for conditions like osteoarthritis and lowers the risk of off-target effects in the liver. In vitro experiments confirm that K9-LNPs promote endosomal escape and efficient expression of mRNA in chondrocytes. Its targeted delivery efficiency is further enhanced by optimizing the LNP formulation (e.g., lipid composition ratios) using a Design of Experiment (DoE) approach. In vivo studies show that after intra-articular injection, K9-LNPs exhibit high biodistribution and gene expression in the knee joint, with limited distribution in major organs like the liver. Therefore, K9 represents an advanced, rationally designed LNP component for achieving joint tissue-specific therapy, providing a key tool for developing targeted mRNA therapeutics.

Lipid M3 is a novel ionizable lipid. Lipid M3's primary role is to enable the efficient co-encapsulation and delivery of CRISPR/Cas9 components—Cas9 mRNA and sgRNA targeting the VEGFA gene—into human retinal endothelial cells. M3 facilitates critical steps for successful gene editing, including stabilizing the nucleic acid cargo, promoting cellular uptake, and enabling effective endosomal escape to release the payload into the cytoplasm. This results in high gene-editing efficiency (indel frequency ~28.7%). A single intravitreal injection of the M3-F4 LNP carrying this CRISPR system demonstrated potent therapeutic effects in mouse models of diabetic retinopathy by significantly inhibiting pathological neovascularization and vascular leakage, while maintaining excellent biocompatibility.

M10 is a piperazine-derived bis-tertiary amine ionizable lipid. With an optimal pKa of 6.56, it enables efficient liver-targeted CRISPR/Cas9 delivery, achieving durable PCSK9 silencing and LDL-C reduction after a single dose, alongside a favorable safety profile.

G9-1 is a nitric oxide (NO)-inhibitory ionizable lipid designed for anti-inflammatory mRNA delivery. Derived from the potent NO inhibitor G9, it retains the ability to suppress macrophage-driven inflammation while enabling efficient mRNA encapsulation and lung-targeted delivery. In a murine acute lung injury model, G9-1 lipid nanoparticles (LNPs) loaded with IL-10 mRNA demonstrated synergistic therapeutic effects by reducing inflammatory cell infiltration, suppressing pro-inflammatory cytokines, and improving systemic tissue injury markers. With its intrinsic immunomodulatory activity and preferential targeting of lung-resident cells, G9-1 represents a promising platform for safer and more effective mRNA therapeutics in inflammatory disorders.

APL-719 is a cationic lipid that can be used to synthesize lipid nanoparticles for drug delivery.

DMDHP ((±)-Dimyristoyl-2,3-dimethylhydroxypropylamine) is a cationic lipid with a polar head group containing a dihydroxy group. DMDHP exhibits superior transfection efficiency and lower toxicity at high DNA doses in mouse intrapulmonary transfection model. DMDHP is commonly used for gene delivery.

SAINT-2 is a cationic lipid with gene transfection activity and is a pyridyl lipid analog. Molecular membranes prepared by SAINT-2 can interact with plasmids to form lipid complexes. After the complex is taken up by cells, the plasmid dissociates from the lipid complex under the action of DOPE and the plasmid translocates across the endosome and/or nuclear membrane. Thus, SAINT-2 effectively transfers small oligonucleotides into cells。

DEA‑14‑DAP is a novel ionizable cationic SORT lipid. As a key component for central nervous system targeting, it enables lipid nanoparticles (LNPs) to specifically target microglia, significantly improving the delivery efficiency and cellular selectivity of nucleic acid drugs in the brain.

Lipid 11 is the optimal ionizable lipid disclosed by Liberate Bio, Inc. in patent WO2025/250730 A1, which can significantly improve the delivery efficiency of nucleic acid drugs to extrahepatic tissues including bone marrow, spleen and muscle, with excellent in vivo stability and safety.

AKG-UO-1 is an innovative ionizable lipid engineered for targeted nucleic acid delivery, exhibiting exceptional hepatic tropism and a high affinity for metabolically active tissues. Leveraging an alpha-ketoglutarate (AKG)-inspired design, it capitalizes on the liver’s high metabolic demand to achieve precise parenchymal accumulation via systemic injection. Crucially, AKG-UO-1 selectively homing into diseased or lipid-accumulated microenvironments, where it enhances endosomal escape and mRNA translation. Its unique degradation pathway actively synergizes with host cells to alleviate metabolic stress and maintain mitochondrial homeostasis, making it an ideal candidate for treating metabolic liver diseases and fatty liver disorders.

HGT5001, disclosed in patent US 2026/0125339 A1 by Translate Bio (now part of Sanofi), is a potent ionizable cationic lipid optimized for mRNA delivery, exhibiting versatile organ tropism governed by the route of administration. When delivered via intratracheal or pulmonary administration, it effectively crosses the mucosal barrier to achieve high transfection efficiency specifically within lung tissues. Conversely, intravenous injection redirects its tropism to the liver and spleen via endogenous ApoE mediation, facilitating systemic protein replacement therapies. Engineered with an optimized headgroup, HGT5001 ensures excellent encapsulation, rapid pH-responsive endosomal escape, and superior biocompatibility with minimal systemic toxicity, making it an exceptional candidate for cystic fibrosis therapies and hepatic treatments.

CA-20 is a bile acid-derived sterol designed to replace cholesterol in mRNA LNPs. It achieves high mRNA encapsulation efficiency up to 87.4% and forms uniform, spherical nanoparticles with ordered membrane structures confirmed by cryo-TEM and MD simulations. In vivo, CA-20 drastically cuts hepatic mRNA expression while shifting nearly all gene expression to the spleen, driven by reduced ApoE protein binding on LNP surfaces. Using HA mRNA vaccines, CA-20 LNPs trigger stronger antigen-specific IgG, neutralizing antibodies, memory B cells and IFN-γ-secreting T cells than cholesterol LNPs. Acute safety tests prove CA-20 causes minimal liver damage, with normal serum liver enzymes and intact organ histology, delivering balanced superior immunogenicity and low liver toxicity for spleen-targeted mRNA vaccine delivery.

Q1-SM-102 iodide is a quaternary ammonium lipid derivative of SM-102. Q1-SM-102 iodide can be used to prepare lipid nanoparticles (LNPs) for the delivery of mRNA in vivo. Q1-SM-102 iodide is a carriers for targeting delivery of mRNA to immune organs.

Lipid 7669 is a premium, spleen-tropic ionizable lipid highly validated in US2025/0049948A1 for targeted mRNA delivery. Engineered for extrahepatic targeting, it achieves exceptional splenic protein expression while minimizing hepatic accumulation, significantly outperforming conventional liver-targeting lipids like MC3 and C12-200. In vivo bioluminescence data confirms its superior whole-body transfection efficiency and highly selective spleen tropism. This high-performance lipid is ideal for pioneering research in mRNA vaccines, splenic immune editing, and autoimmune disease therapies requiring precise extrahepatic delivery. Lipid 7669 is for research purpose.

a12Dab4 is a novel, high-performance peptide-based ionizable lipid designed specifically as the core functional building block for lipid nanoparticles (LNPs) targeting challenging or quiescent cell types, such as human hematopoietic stem and progenitor cells (HSPCs). Chemically engineered to possess a unique peptide-mimetic backbone, it provides superior membrane fusion and exceptional endosomal escape capabilities compared to older-generation, industry-standard lipids like Dlin-MC3-DMA and ALC-0315. Functionally, its primary role within the LNP formulation is to complex and efficiently encapsulate sensitive nucleic acid payloads, such as mRNA or CRISPR/Cas9 editing machinery, at an optimal nitrogen-to-phosphate (N/P) ratio. When formulated, a12Dab4 enables maximum cellular transfection and robust genome editing while exhibiting minimal cytotoxicity and preserving the long-term proliferative, self-renewing functionality of primitive stem cell compartments. Although it delivers commendable baseline transfection independently, it functions as an exceptional molecular chassis that synergies seamlessly with surface antibody conjugation (such as anti-CD34) to unlock precise, therapeutic-grade in vivo gene engineering.

CY7 is an ionizable lipid engineered for localized pulmonary mRNA delivery. Its structure combines a cyclohexane-based core, a 4-dimethylaminopiperidine ionizable headgroup, two ester linkers, and four extended hydrophobic branches. In LNPs formulated with cholesterol, DSPC, and DMG-PEG, CY7 produced substantially higher local luciferase expression and lung-to-liver selectivity than SM-102 following intratracheal administration. CY7 LNPs also enhanced functional mRNA expression in pulmonary neutrophils, endothelial and epithelial cells, as well as dendritic and B cells in lung-draining lymph nodes. When used to deliver PcrV and OprF-I mRNAs, pulmonary CY7 LNP vaccination generated rapid antigen-independent innate protection followed by durable antigen-specific humoral, mucosal, and cellular immunity. In mouse models, it reduced bacterial burden and improved survival following challenge with laboratory and carbapenem-resistant Pseudomonas aeruginosa. CY7 remains a preclinical research lipid requiring further pharmacokinetic, repeat-dose, and translational safety evaluation.

C6O2B2 is a cholesterol-conjugated cationic/ionizable lipid developed for ligand-free mRNA delivery to brain endothelial cells following intravenous administration. Its architecture combines a piperazine-containing polyamine core, four degradable ester-linked hydrophobic tails, and a covalently attached cholesterol moiety through a flexible five-carbon spacer. Among 51 newly synthesized cholesterol-based lipids, C6O2B2 produced the strongest brain luciferase expression. An optimized LNP formulation containing C6O2B2, DODAP, DSPC, and DMG-PEG enabled efficient functional mRNA expression throughout the cerebral vascular network, with preferential transfection of CD31-positive brain endothelial cells and minimal detectable neuronal or glial expression. The formulation preserved BBB integrity in Evans blue and contrast-enhanced MRI assessments. Mechanistic studies associated its activity with improved membrane fusion, enhanced endosomal escape, and ApoA-I enrichment in the protein corona. Delivery of IL-10 mRNA also reduced vascular leakage and inflammatory cytokines in a mouse model of acute neuroinflammation. C6O2B2 remains a preclinical research lipid requiring further pharmacokinetic and repeat-dose evaluation.

CSi12N3 is a bioorthogonally activatable ionizable lipid containing two cleavable silyl-ether-linked C12 tails and a dual-amine headgroup. Formulated as SiLNPs, it remains relatively silent before activation but undergoes Phe-BF3-triggered desilylation, nanoparticle destabilization, and accelerated cytosolic mRNA release. The reported formulation produced up to 44-fold higher mRNA expression than SM-102 LNPs in vitro, with an approximately 10-fold activation-to-silent ratio. In a B16-F10 melanoma model, CSi12N3-based SiLNPs delivering GDNT mRNA induced tumor-localized pyroptosis and inhibited tumor growth without detectable systemic toxicity in the reported study. CSi12N3 is therefore a promising preclinical research lipid for externally controlled, tumor-selective mRNA delivery.

E20 is a charge-switching ionizable lipid developed for efficient nucleic acid delivery with reduced inflammatory toxicity. Its carboxylic acid–tertiary amine headgroup changes charge between acidic formulation conditions and physiological pH, while two hydroxylated spacers and branched 8×6 hydrophobic tails support nucleic acid encapsulation and cytosolic delivery. E20 nanoparticles generated approximately 600 mU/mL serum hEPO after intravenous mRNA administration in mice. Unlike multiple benchmark LNPs, E20 did not exacerbate cytokine production in LPS-pretreated mice or human PBMCs. E20 also enabled sustained pDNA expression without the acute lethality observed with MC3-LNPs and improved IL-22 mRNA treatment in a mouse model of acute lung injury.

EDMPC, a cationic lipid, has an enhanced ability to deliver DNA to pulmonary tissues. EDMPC mediates intralobar DNA delivery to rodents.

Vaxfectin is a cationic lipid-based adjuvant that can be used for plasmid DNA- and protein-based vaccines.

9(10)-Nitrooleate（NOA）is an endogenous nitrated fatty acid that functions as a highly efficient bioactive molecule. Its primary role is the specific inhibition of the STING protein, a key inflammatory signaling sensor within cells. When STING is aberrantly activated, it can trigger a severe inflammatory response, leading to cellular damage.Mechanistically, NOA acts as an electrophile, capable of covalently modifying specific cysteine residues on the STING protein, thereby effectively blocking its ability to activate downstream signaling pathways. This inhibitory action establishes NOA as a potent endogenous anti-inflammatory agent. In practical application, loading NOA into delivery systems, such as lipid nanoparticles, equips them with an intrinsic "molecular fire extinguisher." It significantly mitigates the acute inflammatory response triggered by delivered cargo, effectively transforming otherwise toxic delivery vehicles into safe platforms. The core value of NOA lies in its ability to provide exceptional safety without compromising the functional expression of therapeutic payloads, offering a crucial safeguard for achieving long-term treatments.

TT3 is an ionizable cationic amino lipid that has been used in combination with other lipids in the formation of lipid-like nanoparticles (LLNs). Administration of LLNs containing TT3 and encapsulating mRNA encoding human coagulation Factor IX induces human coagulation Factor IX expression in the plasma of mice.

L-343 is an ionizable cationic lipidoid and can be used to synthetic liposomes for systemic delivery of RNAi therapeutics, Pka: 6.34.L343, with its sterically hindered tert-butyl esters, exhibited slower elimination from plasma and higher and more persistent levels in liver compared with L319.

MVL5 is a new Multivalent Cationic Lipid for siRNA Delivery.Improved total gene silencing and Lower non-specific gene silencing,Lower toxicity.

BAMEA-O16B, a lipid nanoparticle integrated with disulfide bonds, can efficiently deliver Cas9 mRNA and sgRNA into cells while releasing RNA in response to the reductive intracellular environment for genome editing as fast as 24 h post mRNA delivery.

C13-112-tetra-tail is an advanced ionizable lipid molecule designed for use in lipid nanoparticles (LNPs) to deliver anionic substrates, such as nucleic acids (e.g., siRNA, mRNA) or proteins, both in vitro and in vivo.

16:0 TAP is a cationic derivative of trimethylammonium linked with two 16-carbon fatty acid tails. 16:0 TAP is a cationic liposome-forming compound that may be used for transfection of DNA, RNA, and other negatively charged molecules into eukaryotic cells. Reagent grade, for research use only.

Dioleyldimethylammonium chloride (DODAC) is a cationic lipid that can be used as transfection reagent.

DOBAQ, N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propan-1-aminium, is a cationic lipids with a quaternary amine and unsaturated hydrocarbon chains. DOBAQ also serves as a pH-sensitive transfection reagent. Reagent grade, for research use only.

IR-117-17 (A10-LIN) is an ionizable and biodegradable lipid specifically designed for nebulized mRNA delivery. When formulated into lipid nanoparticles (LNPs), IR-117-17 demonstrates remarkable efficacy, achieving a 300-fold enhancement in lung mRNA delivery compared to the best-performing LNP previously reported. Additionally, it shows a two-fold improvement over the leading PBAE-based delivery system, with up to a 45-fold increase in mRNA delivery efficiency to the large airways.

Butanoic acid, 4-(dimethylamino)-, di-(9Z,12Z)-9,12-octadecadien-1-ylazanyl ester is listed as a ionizable lipid for laboratory research use.

BP-26383 is listed as a ionizable lipid for laboratory research use.

BP-26410 is listed as a ionizable lipid for laboratory research use.

BP-28671 is listed as a ionizable lipid for laboratory research use.

LNP Lipid-2 is a lipid product can be used to deliver agents.

SM-102 Analog 2(Compound 8-8) is a lipid compound. SM-102 Analog 2(Compound 8-8) is involved in the synthesis of lipid nanoparticles compositions. SM-102 Analog 2(Compound 8-8) has potential applications in the transportation of biologically active substances.

DOSPA is a cationicliposome. DOSPA can formulate with DNA to be a transfection system. DOSPA can be used for gene therapy research.

Genevant CL1 monohydrochloride, an ionizable lipid with a pKa of 6.3 (also referred to as lipid 10), serves as a key component in the formulation of lipid nanoparticles (LNPs) for the delivery of mRNA vaccines.

GL67 (N4-Spermine cholesteryl carbamate) in its pentahydrochloride form is a cationic lipid with versatile applications in the delivery of nucleic acid agents, vaccines, and gene transfection, owing to its efficient encapsulation and transport capabilities.GL67 (N4-Spermine cholesteryl carbamate) in its pentahydrochloride form is a cationic lipid with versatile applications in the delivery of nucleic acid agents, vaccines, and gene transfection, owing to its efficient encapsulation and transport capabilities.

A12-Iso5-4DC19 is a cationic lipid with ionizable properties, designed to enhance mRNA delivery efficiency. Its unique structure makes it a promising candidate for developing advanced RNA-based vaccines and therapeutics.

A1-EP10-O18A​​ is an ​​asymmetric ionizable lipid​​ developed by Starna Therapeutics for mRNA vaccine delivery. Synthesized via Michael addition between amine alcohols and acrylates, its optimized structure—combining a hydrophilic C10 chain and hydrophobic unsaturated C18 tail—enables pH-dependent ionization. As the core component of the ​​STAR0225 lipid nanoparticle (LNP)​​ platform, it efficiently encapsulates mRNA and facilitates endosomal escape. Preclinical studies demonstrate superior in vivo mRNA delivery (vs. commercial SM102 LNPs), with enhanced local biodistribution and minimal off-target accumulation. This lipid underpins ​​STR-V003​​, an RSV prefusion F mRNA vaccine showing robust immunogenicity and protection in animal models, supporting its clinical transition (NCT06344975).

OF-Deg-Lin is a biodegradable lipid containing an ester group, developed from the nonbiodegradable, linoleic acid derived OF-02; mRNA-LNPs containing OF-Deg-Lin showed high expression in the spleen.

ATX-001 is a novel ionizable cationic lipid compound for RNA delivery.

A-066 is listed as a ionizable lipid for laboratory research use.

R-DOTAP(DOTAP R-isomer) is listed as a ionizable lipid for laboratory research use.

S14 is listed as a ionizable lipid for laboratory research use.

SM-102 IMPURITY 1 is listed as a ionizable lipid for laboratory research use.

E4i-200 is a branched ionizable lipid designed for efficient mRNA and CRISPR-Cas9 delivery. It features a 4-carbon (C4) lipid tail with an isopropyl (i) branch at the terminal position, enhancing its ability to disrupt endosomal membranes. The lipid is built around the 200 core, a polyamine structure (N1-(2-(4-(2-aminoethyl)piperazin-1-yl)ethyl)ethane-1,2-diamine), which facilitates mRNA encapsulation and delivery. E4i-200 excels in liver-targeted delivery, significantly improving mRNA translation and gene editing efficiency in vivo. In experiments, it outperformed linear lipids, achieving 1.5-fold higher liver luminescence compared to the gold standard C12-200. Its isopropyl branch promotes deeper membrane penetration, enhancing endosomal escape and cargo release. This lipid is particularly effective for hepatic gene editing, reducing target gene expression (e.g., TTR) by up to 90% in mouse models. Its modular design and low toxicity make it a promising candidate for mRNA-based therapies and CRISPR applications in the liver.

E8i-200 is a novel Branched Endosomal Disruptor (BEND) ionizable lipid, designed to enhance the efficiency of lipid nanoparticles (LNPs) in drug delivery, particularly for mRNA and protein delivery. Its unique structure, featuring terminal branching, improves endosomal escape, a critical step in the delivery of therapeutic cargo into cells.E8i-200 is designed to enhance endosomal escape, a key bottleneck in mRNA and protein delivery. Its terminal branching structure provides several advantages:Improved Endosomal Membrane Penetration: The branched structure allows E8i-200 to more effectively disrupt endosomal membranes, facilitating the release of mRNA and proteins into the cytoplasm.Enhanced Gene Editing Efficiency: E8i-200 has been shown to significantly improve the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes, enabling efficient gene editing in vivo.E8i-200 significantly enhanced mRNA expression in the liver, outperforming traditional linear lipids like C12-200 in mouse models.E8i-200 effectively delivered CRISPR-Cas9 RNP complexes, achieving high editing efficiency in the liver, surpassing that of linear lipids.E8i-200 also showed high transfection efficiency and low cytotoxicity in T cells, making it a promising candidate for CAR-T cell engineering and other immunotherapies.

ATX-002 is a property-tunable lipid for RNA drug delivery.

DODAP (hydrochloride) is an ionizable lipid. DODAP (hydrochloride) has the potential for the research of gene delivery.

DMRIE is a cationic lipid, suitable for transfecting DNA and RNA into eukaryotic cells, and is particularly effective for transfecting suspension cells (e.g., Jurkat) and other lymphoid-derived cell lines.

DLin-K-DM4 is listed as a pegn for laboratory research use.

DlenDMA is a lipid for RNA and vaccine delivery. DLenDMA showed better siRNA transfection efficiency than DODMA.

BGTC is listed as a ionizable lipid for laboratory research use.

DLinDAP is listed as a ionizable lipid for laboratory research use.

C2-DLinDMA is listed as a ionizable lipid for laboratory research use.

DLin-K-C4-DMA is listed as a ionizable lipid for laboratory research use.

C13-112-tri-tail is a synthetic ionizable lipid molecule designed for use in lipid nanoparticles (LNPs) for the delivery of anionic substrates, such as nucleic acids (e.g., siRNA, mRNA) and proteins.

C13-113-tri tail is an ionizable lipid molecule containing a polar amino alcohol head group, three hydrophobic carbon-13 tails, and a tertiary amine linker. The lipoid can be formulated into a lipid nanoparticle (LNP) to deliver anionic substrates in vitro and in vivo. This includes siRNA to induce gene silencing in a sequence-specific manner, CAS9 mRNA, and cytotoxic proteins. Reagent grade, for research purpose. Please contact us for GMP-grade inquiries.

C13-113-tetra-tail is an ionizable lipid molecule designed for use in lipid nanoparticles (LNPs) for the delivery of therapeutic payloads, such as nucleic acids (e.g., siRNA, mRNA) or proteins.

TAP (14:0) A cationic lipids that can be used for drug delivery, gene transfection and vaccine delivery. TAP has been proven to be efficient for in vitro and in vivo transfection applications, which makes it one of the most widely used cationic lipids for gene transfection applications. Reagent grade, for research use only.

DC-6-14 is a cationic lipid that can be used for drug delivery, gene transfection and vaccine delivery. DC-6-14 may be used for research into in vitro and in vivo nucleic acid and protein delivery. Reagent grade, for research use only.

16:0 DAP, 1,2-dipalmitoyl-3-dimethylammonium-propane, is a cationic lipid that can be used to formulate lipid nanoparticles (LNPs). 18:0 DAP also serves as a pH-sensitive transfection reagent. Reagent grade, for research use only.

RM133-3 is an ionizable lipid for potent functional mRNA delivery in vivo. The LPN formulation RM133-3-21, is found to be roughly 4.5 times more potent than DLin-MC3-DMA.

Lipid R6 is an AGILE-identified ionizable lipid for macrophage mRNA delivery research. Its acyclic diethylaminopropyl headgroup is linked to an asymmetric, saturated amino-amide scaffold. R6 LNPs supported higher mRNA-derived expression than H9 and MC3 LNPs in RAW 264.7 macrophages in the cited study. The reported GFP-positive population was 51.0% under the specified in vitro conditions. Its activity was cell-type dependent: H9 performed better in HeLa cells and muscle delivery. R6 is supplied as the lipid building block; formulation-specific results and composition discrepancies are detailed below.

H9 is a new ionizable lipid driven from AI-Guided Ionizable Lipid Engineering (AGILE) platform for mRNA delivery. H9 LNPs shows superior mRNA transfection potency compared to LNPs containing (D-Lin-MC3-DMA).

C12-TLRa is an adjuvant lipidoid. C12-TLRa substitution can enhance the immunogenicity of clinically relevant SARS-CoV-2 mRNA-LNP vaccines, which holds translational potential.

Lipid 16 is an ionizable lipid that can be used to synthesize lipid nanoparticles (LNP) for delivering mRNA and other payloads. Lipid 16 as a potent cell type-specific ionizable lipid for the CD11bhi macrophage population without an additional targeting moiety.

OC2-K3-E10 is an ionizable cationic lipid (pKa = 6.8).1 It has been used in the formation of lipid nanoparticles (LNPs) for the delivery of CRISPR complementary single-guide RNA (sgRNA) and Cas9 mRNA for genome editing in transgenic mice.

1O14 is an ionizable cationic lipid that has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs).

Lipid catechol is a lipid that contains an α-aminophosphonate group, two 14-carbon acyl chains, and a catechol ring that forms a covalent bond with boronic acid-containing compounds to form lipid prodrug nanoassemblies (LPNA).1 LPNAs composed of lipid catechol conjugated to phenylboronic acid-modified ciprofloxacin (CIP-PBA) inhibit the formation of, and disrupt preformed, S. aureus biofilms and eradicate staphylococci in a mouse model of peritoneal S. aureus infection. LPNAs composed of lipid catechol conjugated to bortezomib (BTZ) reduce tumor growth and increase survival in a 4T1 murine mammary carcinoma model.

DIM7S is a sugar-alcohol-derived ionizable lipid with mannitol as the precursor. DIM7S LNP is 10-fold, 30-fold, 20-fold, 4-fold and 3-fold superior in mRNA delivery than Lipo 3K, Electro, ALC-0315, MC3 and SM-102, respectively. DIM7S LNP enables effective CD40 mRNA delivery into human peripheral blood monocyte-derived DCs without obvious cytotoxicity.

LIS10W is a sugar-alcohol-derived ionizable lipid with L-sorbitol as the precursor.

IAJD 288(IAJD-288) is a pentaerythritol-based one-component ionizable amphiphilic Janus Dendrimer (IAJD), delivery systems for mRNA delivery.

CL1H6 is an ionizable lipid designed for advanced nucleic acid delivery, and its lipid nanoparticle formulation, CL1H6-LNP, demonstrates exceptional efficiency in delivering both siRNA and mRNA into NK-92 cells. This innovative system enables precise and effective intracellular delivery, making it a valuable tool for enhancing therapeutic and research applications in natural killer cell biology.

244cis is listed as a ionizable lipid for laboratory research use.

IR-19-Py(A20-0l) is listed as a ionizable lipid for laboratory research use.

C14-O2 is an oxidized lipid for mRNA delivery. C14-O2-LNP is capable of potent and selective delivery of mRNA to blood monocytes. C14-O2 LNP is used to deliver a functional CD19-CAR mRNA and is shown to engineer functional CAR monocytes directly in situ.

Lipid CAD9 (3-A2-7b is a cationic degradable (CAD) lipid. 3-A2-7b formulated LNP, LNP-CAD9, can deliver FLuc mRNA to the lungs in vivo. LNP-CAD9 co-delivering Cas9 mRNA/VEGFR2 single guide RNA (sgRNA) effectively induces VEGFR2 knock out in lung endothelial cells of female mice.

TE-EP8-S is a single-component, ionizable cationic lipid designed specifically for the targeted delivery of mRNA to T cells within the spleen. This innovative lipid formulation enhances the efficiency and precision of mRNA-based therapies by ensuring optimal cellular uptake and expression in immune cells. Its unique structure and properties make it a promising tool for advancing immunotherapeutic applications.

H1L1A1B3 is an ionizable lipid which demonstrates a fourfold increase in circRNA transfection efficiency in lung cancer cells over ALC-0315. H1L1A1B31 is capable of proactively stimulating innate immune activation upon injection.

O12-D3-I3 is an imidazole-based lipid for siRNA delivery. O12-D3-I3-LNPs encapsulating FVII siRNA (FVII@O-LNP) elicites greater gene silencing than those with the DLin-MC3-DMA (MC3) due to its stronger endosomal escape.

12T-O14 is a amidine-incorporated degradable (AID) lipid for versatile mRNA delivery. 12T-O14-LNPs mediate efficient intramuscular delivery of mRNA vaccines and systemic delivery of mRNA therapeutics without noticeable toxicity. 12T-O14 serves as a superior supplementary lipid to redirect liver-tropic LNPs to selectively target the lung or spleen via simple adjustment of the formulation.

TG6A is a biodegradable and ionizable glycerolipid for cmRNA delivery. TG6A-LNP exhibits above 9-fold and 41-fold higher EGFP protein expression in MSCs than DLin-MC3-DMA-LNP and ALC-0315-LNP, respectively.

Si6-C14b is a siloxane-incorporated lipid for livertargeting mRNA delivery. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy.

Si12-C10 is a siloxane-incorporated lipid for spleen-targeting mRNA delivery. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy.

CL4F11_ζ-2 is an ionizable lipid for hepatic delivery of CRISPR/Cas ribonucleoprotein (RNP). CL4F11_ζ-2 LNP shows an extremely strong inhibitory effect of serum TTR protein levels compared with all the approved ionizable lipids including DLin-MC3-DMA (MC3), SM-102, and ALC-0315.

THP1 is a tetrahydropyrimidine ionizable lipid for mRNA delivery. THP1 demonstrates higher transfection efficiency comparable to DLin-MC3-DMA (MC3). THP1 LNPs also demonstrates the ability to edit genes in specific liver tissues in a tdTomato transgenic mouse model.

(+)CP-LC-0729 is an cationic lipid derived from CP-LC-0729 and achieves significantly higher expression and selectivity highlights the advantages of this lipid system for lung-targeted delivery.

Lipid I97 is a vitamin B5-derived ionizable lipid for mRNA vaccine delivery. Lipid I97 LNP specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies with low toxicity.

313O13 is an ionizable lipid with amine headgroups which drives LNP immunogenicity by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation. 313O13 prevents the often-observed loss of efcacy in the LNP-mediated delivery of siRNA and mRNA.

313oi10 is an ionizable lipid with amine headgroups which drives LNP immunogenicity by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation. 313oi10 prevents the often-observed loss of efcacy in the LNP-mediated delivery of siRNA and mRNA.

31hP is an asymmetric A3-lipid for mRNA delivery. 31hP LNP exhibits higher stability and durability compared with MC3 LNP and SM-102 LNP. 31hP LNP achieves more efficient hepatic mRNA delivery with a much higher gene editing efficiency than MC3 LNP and LP01 LNP.

A2C18_D5 is an optimized lipid nanoparticle (LNP) component engineered with structural modifications to enhance mRNA delivery efficiency and safety. Its design incorporates a hydrophobic head group (A2, featuring a pentyl chain) and an unsaturated C18 tail, which collectively lower its pKa to the ideal range of 6–7, enabling stable encapsulation of nucleic acids and improved endosomal escape. In vitro and in vivo studies demonstrate that A2C18_D5 achieves mRNA delivery efficiency comparable to the clinically approved LNP benchmark MC3, while exhibiting over 200-fold higher potency than its precursor lipid (A1C11). The lipid’s reduced protonation capacity minimizes cytotoxicity and hemolytic risk, aligning with safety profiles of established LNPs. Upon intravenous administration, A2C18_D5 predominantly targets the liver and spleen, with a biodistribution profile favoring hepatic delivery. Its balanced combination of high transfection efficiency, low toxicity, and favorable pharmacokinetics positions A2C18_D5 as a promising candidate for next-generation mRNA therapeutics, including vaccines and treatments for liver-specific diseases. Further optimization of its head-tail structure highlights its versatility for tailored delivery applications.

A3T2C7 (CP-LC-1495) is a biodegradable ionizable lipid featuring three β-propionate linkers and an azetidine polar head, formulated in four-component LNPs. It demonstrates exceptional lung-targeted mRNA delivery with 97.1% selectivity and high protein expression (1.21×10⁸ p/s) in mice. Its slightly positive zeta potential (~3.5 mV) correlates with lung tropism, likely mediated by protein corona enrichment of vitronectin and prothrombin. The β-propionate structure enables pH-sensitive biodegradability for enhanced endosomal escape while maintaining low cytotoxicity (>90% cell viability). This lipid enables organ-specific mRNA delivery without permanently charged additives, outperforming conventional SORT strategies in selectivity and expression efficiency.

F11T6 is a next-generation lipid nanoparticle (LNP) optimized for ultra-efficient neuron-targeted mRNA delivery, featuring a dual-tetrahydrofuran (THF) core and four pH-responsive acetal tails. Its unique bis-THF architecture enhances lipid bilayer stability and promotes brain-specific biodistribution, achieving ​​16.4% GFP+ neurons​​ in vivo—the highest reported among CNS-targeting LNPs. Cryo-EM reveals a compact spherical structure (Ø~150 nm) with 93.2% mRNA encapsulation efficiency, while THF-acetal synergy enables rapid endosomal escape (Pearson coefficient: 0.16 vs. 0.27 for F10T5). Preclinical studies show F11T6 leverages meningeal lymphatic transport for brain accumulation, yielding ​​13.0% neuron-specific tdTomato expression​​ in Ai14 mice, surpassing F10T5 (8.93%) and SM102 (0.1%). Mechanistically, the dual-THF core strengthens interactions with lipoprotein receptors on brain endothelial cells, whereas acetal tails undergo acid-triggered hydrolysis in endosomes, releasing mRNA into the cytoplasm. Despite slightly higher liver/spleen accumulation than F10T5, toxicology assessments confirm no hepatorenal toxicity (BUN/ALT/AST within normal ranges) or histopathological changes. Co-localization analyses demonstrate superior penetration into deep brain regions like the hippocampus, critical for treating neurodegenerative disorders. With a LogD of 12.3, F11T6 balances lipid solubility and biodegradability, outperforming clinical benchmarks in both efficiency (40× SM102) and neuron specificity. This platform holds transformative potential for delivering CRISPR-Cas9, siRNA, or neurotrophic factors, particularly in diseases demanding high-dose CNS transfection with minimal off-target effects.

THOR 76​​ is an ionizable lipid developed for lung-targeted mRNA delivery, synthesized via a high-throughput Ugi four-component reaction (U4CR). It combines spermine (N3, amine core), oleyl aldehyde (A2), oleic acid (C2), and a morpholine-functionalized isonitrile (D3). Remarkably, its ​​crude reaction mixture​​ outperforms purified forms in efficacy, suggesting synergistic impurities or intermediates enhance function. Formulated into lipid nanoparticles (LNPs) with cholesterol, DOPE, and PEG-lipid, THOR 76 LNPs exhibit ​​exceptional lung tropism​​ with secondary spleen affinity after intravenous administration. They efficiently transfect ​​pulmonary endothelial cells​​, enabling robust gene expression (e.g., Cre recombinase) and significant CRISPR-Cas9-mediated gene editing (1.22% at 0.1 mg/kg dose) in the lungs. With a particle size <150 nm, positive zeta potential, and >90% mRNA encapsulation, THOR 76 achieves targeted delivery while minimizing off-target effects in the liver. Its design overcomes limitations of cationic helper lipids, offering a potent, tolerable platform for treating pulmonary genetic disorders and cancers.

A33-D268 is an ionizable lipid derived from a 2-aminoimidazole (AM) core, featuring an asymmetric hydrophobic tail structure designed to optimize mRNA interactions. Selected as the top candidate from a 21-lipid library through molecular dynamics (MD) simulations, it demonstrated superior performance: low root mean square deviation (RMSD) and the smallest radius of gyration (Rg), indicating tight mRNA compaction, alongside moderate electrostatic energy and above-average hydrogen bonding for stable encapsulation. Formulated into LNPs, it achieves ​​efficient muscle-specific transfection​​ post-intramuscular injection, rivaling commercial ALC-0315 LNPs. Crucially, it exhibits ​​29-fold lower hepatic off-target expression​​, attributed to its inability to leverage serum protein coronas for liver tropism.

4A3-Cit is an ionizable lipid used for the generation of lipid nanoparticles (LNPs). To investigate the role of unsaturated lipid tails in iLNPs, the nucleophilic amines were added to ester-based linkers, followed by Michael’s addition to the thiols to construct a library of 91 amino ionizable lipids. Such ionizable lipids were composed of an ionizable tertiary amine core, an ester-based degradable linker, and an alkylthiol tail periphery. Through in vitro and in vivo screening, the iLNPs with 4A3 core and citronellolbased (Cit) periphery can significantly increase endosome escape and delivery efficiency of mRNA, leading to 18-fold increase in protein expression compared with iLNPs without Cit periphery. Furthermore, the delivery efficiency of mRNA may be associated with the location/configuration of the unsaturated bond(s) in lipids. Although lipids with Cit periphery showed excellent membrane fusion ability to facilitate endosome escape, the fusion mechanism needs to be further clarified.

G0-C14 is listed as a ionizable lipid for laboratory research use.

AL-A12 is an ionizable cationic amino lipid that has been used in the formation of lipid nanoparticles (LNPs).1 LNPs containing AL-A12 and encapsulating minicircle DNA that encodes for GFP have been used to induce GFP expression in Huh7 cells.

Lipid 1 is an ionizable amino lipid used for the generation of Lipid nanoparticles (LNPs).

LNP Lipid-5 (Compound Lipid 2) is an ionizable lipid (amino lipid). LNP Lipid-5 can be used to prepare lipid nanoparticles .

DOG-IM4 is an ionizable cationic lipid (apparent pKa = 5.6) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA.1 Immunization with LNPs containing DOG-IM4 and encapsulating mRNA encoding influenza A hemagglutinin (HA) increases HA-inhibiting antibody titers (HI titers) in mice and cynomolgus macaques.

Bis(N-2-ethoxyethyl 2-hexyldecanoate)amine is a cationic lipid-like PEG compound containing a polar alcohol head group, four hydrophobic tails bound by esters, and a tertiary amine linker. The hydrophilic PEG linker increases the water solubility of the compound in aqueous media. Reagent grade, for research purpose. Please contact us for GMP-grade inquiries.

LNP Lipid-6 (Compound Lipid 5) is an ionizable lipid (amino lipid). LNP Lipid-6 can be used to prepare lipid nanoparticles (LNP).

cKK-E15 is an ionizable cationic lipid and a derivative of cKK-E12 that has been used in the generation of lipid nanoparticles (LNPs).1 LNPs containing cKK-E15 and encapsulating Cre mRNA induce the expression of Cre in Kupffer cells, endothelial cells, and hepatocytes in Ai14 mice engineered to express the fluorescent protein tdTomato upon translation of Cre.

1,2(R)-Dioleyloxy-3-dimethylamino-propane ((R)-DODMA) is an ionizable cationic lipid and an isomer of DODMA

306Oi9-cis2 is an ionizable cationic lipid. WARNING This product is not for human or veterinary use.

Lipid AX4 is an ionizable cationic lipid (pKa = 6.89) that has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA in vivo.

RM 137-15 is an ionizable cationic lipid that has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA in vivo.

C12-SPM is a polyamine branched-chain lipidoid.

C14-SPM is a polyamine branched-chain lipidoid.1 It has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs) for the delivery of siRNA.

C3-K2-E14 is an ionizable cationic lipid (pKa = 5.5).1 It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA or siRNA in vitro and in vivo.

(S)-C12-200 is an ionizable cationic lipid (pKa = 7.12) and an isomer of C12-200 (Item No. 36699).1 It has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA in vivo.

PPPDA-O16B is a disulfide bond-containing ionizable cationic lipid that has been used in the generation of lipid nanoparticles (LNPs) for plasmid delivery in vitro and in vivo.

BAmP-O16B is an ionizable cationic amino lipid that has been used in the generation of lipid nanoparticles (LNPs).

Lipid OA2 is an ionizable cationic lipid that has been used in the generation of single-component lipid nanoparticles (LNPs) for the delivery of siRNA.

Ionizable lipid 4 is an ionizable cationic lipid (pKa = 6.1) and a hydrogen peroxide-induced rearrangement product of the cationic lipid CA-lipid 5.1 Charge-altering lipid nanoparticles (CALNPs) containing CA-lipid 5 and encapsulating siRNA against EGFP undergo hydrogen peroxide-induced removal of the phenylboronic acid groups from CA-lipid 5 in MCF-7 cells in vitro, generating ionizable lipid 4-containing LNPs with reduced positive charges at physiological pH, facilitating intracellular siRNA release and gene silencing. LNPs containing ionizable lipid 4 and encapsulating siRNA against PLK1 reduce tumor volume in an MCF-7 mouse xenograft model less effectively than CALNPs containing CA-lipid 5.

E12CA1A3 is an ionizable cationic lipid (pKa = 6.4) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA in vitro and in vivo.1 LNPs containing E12CA1A3 and encapsulating an mRNA reporter induce luciferase reporter expression in mouse bone marrow-derived dendritic cells (BMDCs) and mice. LNPs containing E12CA1A3 are cleared more rapidly from the liver than LNPs containing DLin-MC3-DMA (Item No. 34364) in mice.

SIL lipid is an ionizable cationic lipid that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA in vitro.1 LNPs containing SIL lipid and encapsulating siRNA targeting mRNA encoding the purinergic P2X7 receptor decrease protein levels of the purinergic P2X7 receptor, reduce migration in a wound healing assay, and induce apoptosis and necrosis in 4T1 breast cancer cells.

DDAB, also known as dodecyltrimethylammonium bromide, is a cationic surfactant with specific solubility, stability, and storage conditions. 1. Solubility: DDAB is soluble in water and organic solvents such as ethanol and chloroform. It forms clear solutions in water, but can become turbid at high concentrations or low temperatures. It has a higher solubility in organic solvents compared to CTAB. 2. Stability: DDAB is relatively stable under normal storage conditions. However, it can undergo degradation and lose its surfactant properties if exposed to extreme temperatures, humidity, or oxidizing agents for extended periods. It is important to store DDAB in a cool, dry place away from direct sunlight. 3. Storage conditions: DDAB should be stored in a tightly sealed container to prevent moisture absorption and contamination. It is recommended to store it at room temperature (around 20-25°C) or in a refrigerator (2-8°C) to maintain its stability and extend its shelf life.

Al-28 is a multi-ionizable aminolipid featuring a central amine and three identical disulfide-linked saturated side chains. The hydrophobic side chains are linked to the central structure by ester as well as disulfide bonds. Disulfide bonds are readily cleaved in the reducing environment of the cell cytoplasm. Ionizable lipids are typically used in the design of nucleic acid lipid nanoparticles, as their pH-dependent positive charge stabilizes the anionic nucleic acids they encapsulate.

9A1P9 is a multi-tail ionizable cationic phospholipid. 9A1P9 induces membrane destabilization. 9A1P9 can be used for CRISPR-Cas9 gene editing in mice.

ALC-0315 analogue-1 (compound P-10) is a cationic lipid. ALC-0315 analogue-1 is the raw material for synthesis of cationic liposome.

Lipid CP-LC-1143 is an ionizable cationic amino lipid derived from homocysteine, a naturally occurring amino acid. This lipid has demonstrated an efficient delivery and high protein expression of different kinds of RNA (mRNA, cRNA and saRNA) in vivo, with no signs of toxicity.

Lipid CP-LC-0729, an ionizable cationic amino lipid synthesized from homocysteine—a naturally occurring amino acid—has been shown to exhibit superior efficacy in the delivery and subsequent protein expression of various RNA modalities, including messenger RNA (mRNA), circular RNA (cRNA), and self-amplifying RNA (saRNA) in vivo. Importantly, CP-LC-0729 demonstrates an exemplary safety profile, with no observable toxicological effects in preclinical studies. Comparative analyses reveal that CP-LC-0729 significantly surpasses MC3, a widely utilized benchmark lipid nanoparticle formulation, in terms of protein expression efficiency. Specifically, CP-LC-0729 achieves a striking 32-fold enhancement in protein expression within lung tissue relative to MC3, underscoring its pronounced tissue selectivity and targeting efficacy for pulmonary applications. These findings suggest that CP-LC-0729 represents a highly promising candidate for the development of RNA-based therapeutics, particularly in the context of lung-targeted delivery systems, where its combination of high efficiency and low toxicity offers significant translational potential.

Lipid CP-LC-0743 is an ionizable cationic amino lipid derived from homocysteine, a naturally occurring amino acid. This lipid has demonstrated an efficient delivery and high protein expression of different kinds of RNA (mRNA, cRNA and saRNA) in vivo, with no signs of toxicity.

CP-LC-0867 is listed as a ionizable lipid for laboratory research use.

C9-200 is an ionizable cationic lipid that has been used in the formation of lipid nanoparticles (LNPs). LNPs containing C9-200 and encapsulating mRNA encoding erythropoietin (EPO) increase serum EPO levels in mice. LNPs containing C9-200 and encapsulating mRNA encoding the Cas9 nuclease and small-guide RNA (sgRNA) targeting transthyretin (TTR) induce 3-fold higher hepatic insertion and deletion (indel) formation than LNPs containing C12-200 and encapsulating mRNA encoding Cas9 in mice.

YHS-12 is an ionizable cationic lipid (pKa = 6.506) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA and mRNA in vitro and in vivo.1 LNPs containing YHS-12 and the macrophage targeting peptide CRVLRSGSC and encapsulating mRNA encoding chimeric antigen receptor targeting methicillin-resistant S. aureus (MRSA) and siRNA targeting caspase-11 increase the phagocytosis rate of MRSA in RAW 264.7 macrophages and primary mouse bone marrow-derived macrophages (BMDMs). Intravenous administration of these LNPs decreases blood bacterial burden and increases survival in a model of sepsis using cyclophosphamide-induced immunosuppressed mice.

113-N16B is an ionizable cationic lipid used for the generation of lipid nanoparticles (LNPs). 113-N16B delivers mRNA preferentially to pulmonary endothelial cells.

1-A-N is a lipid nanoparticle (LNP) used for in vivo delivery of siRNA. 1-A-N can regulate immune response by delivering siCD45 (siRNA targeting CD45) to T cells and silencing the CD45 gene.

Lipid 50 (compound 50) is an ionizable lipid that can be used for the generation of lipid nanoparticles (LNPs). Lipid 50 is a carrier for both siRNA and mRNA.

Ionizable lipid Az1 is listed as a ionizable lipid for laboratory research use.

Lipid DIM1 is an ionizable cationic lipid that has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs) for mRNA delivery in vitro.1 LNPs containing lipid DIM1 and encapsulating mRNA encoding a luciferase reporter induce luminescence in primary mouse adipose stem cells (ASCs).

IZ-Chol (IZ-Cholesterol) is an ionizable cationic lipid containing cholesterol. IZ-Chol-LNPs is highly potential to effectively complex with DNA, and endosome escape mechanisms mediated by proton sponge effect.

Cho-es-Lys is listed as a ionizable lipid for laboratory research use.

Lipid B37 (B37) is an ionizable amino lipid, which can be used to form lipid nanoparticles and deliver mRNA.

4-O10b1 is an ionizable lipid used to generate lipid nanoparticles (LNPs) for delivering RNA to cells. LNPs comprised of 4-O10b1 and conjugated with the macrophage antibody F4/80 were able to delivery siRNA targeting TAK1 to RAW264.7 cells resulting in suppressed activation of NF-kB. Intranasal administration reduced lung injury in an influenza mouse model.

Lipid 35 is an novel ionizable lipid designed to enhance the delivery of mRNA to specific tissues, particularly the lungs.Lipid 35 demonstrates superior chemical stability, especially in storage conditions. This stability ensures that the lipid maintains its integrity over extended periods, making it ideal for long-term storage and large-scale production.Lipid 35 exhibits high transfection efficiency in various cell types, including nonimmune cells, endothelial cells, and epithelial cells. Lipid 35 has demonstrated excellent biocompatibility and safety in preclinical studies. It does not cause significant liver damage or adverse immune responses, making it a safer alternative for therapeutic applications.

L-608 is a novel ionizable amino lipid designed for formulating lipid nanoparticles (LNPs) to enable efficient subcutaneous (s.c.) delivery of mRNA therapeutics. Engineered to address inflammation associated with mRNA LNPs, L608 integrates seamlessly with steroid prodrugs, such as budesonide-C16 and budesonide-C18:1, to suppress local and systemic inflammatory responses while prolonging therapeutic protein expression. Preclinical studies demonstrate that L608 LNPs significantly reduce injection-site edema (>80% improvement) and lower systemic inflammatory markers (e.g., haptoglobin), while achieving 2–3× higher plasma AUC for proteins like hFGF21 compared to non-steroid LNPs.

C14-490 is an ionizable cationic lipid (pKa = 5.94).1 It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA in vivo.C14-490-containing LNPs accumulate primarily in the fetal mouse liver and, to a lesser extent, in the lungs, intestine, and brain after vitelline vein injection on gestational day 16 (E16).1 CD45-functionalized LNPs containing C14-490 and encapsulating mRNA encoding GFP transfect Jurkat cells, which constitutively express the CD45 receptor (CD45R).C14-490-containing CD45-functionalized LNPs encapsulating Cre mRNA mediate genome modulation in bone marrow hematopoietic stem cells (HSCs) for at least four months after in utero injection in R26mT/mG mice at E13.5.

ATX-231 which is from Arcturus RNA delivery platform, is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA.

Lipid B1​ is a next-generation ionizable lipid engineered for superior mRNA delivery, featuring a patented ​β-isobutylglutarate branching linker​ that optimizes nanoparticle assembly and intracellular release. Its unique structure combines a pH-responsive tertiary amine headgroup with twin C18 alkyl tails connected via biodegradable ester bonds, enabling precise control over lipid packing and endosomal escape. Preclinical studies demonstrate that Lipid B1-based LNPs (bLNPs) achieve ​**>75% transfection efficiency in vitro​ at ultra-low mRNA doses (1 μg), outperforming commercial benchmarks like SM-102. In vivo, subcutaneous administration of bLNPs delivers ​10-fold higher luciferase expression**​ than linear-chain analogs, with targeted biodistribution to lymph nodes and tumor sites. Clinically relevant data show 100% tumor prevention in prophylactic cancer vaccine models and 70% tumor regression in therapeutic settings when combined with checkpoint inhibitors. The ester-based backbone ensures rapid metabolic clearance, minimizing systemic toxicity risks (NOAEL >10 mg/kg in mice). Compatible with mRNA, siRNA, and CRISPR-Cas9 payloads, Lipid B1 is ideal for vaccines, gene therapies, and immuno-oncology. Its scalable 3-step synthesis (yield >80%) and lyophilization stability (-80°C, 12 months) make it a cost-effective solution for GMP-grade production. For advanced delivery with unmatched safety and efficacy, Lipid B1 sets a new standard in nucleic acid therapeutics.

AA2 lipid is an innovative amino alcohol-derived ionizable lipid designed for optimized mRNA delivery. Its unique structure includes a hydroxyl-containing headgroup that enhances mRNA binding through hydrogen bonds and a branched ester tail (R2) that promotes a cone-shaped architecture, facilitating efficient endosomal escape. Formulated into lipid nanoparticles (LNPs) with a size of 108.6 ± 3.7 nm and a polydispersity index (PDI) below 0.3, AA2 achieves high mRNA encapsulation efficiency (89.0 ± 1.4%) and an ideal pKa of approximately 6.2, ensuring effective endosomal release.In vivo studies demonstrate that AA2 LNP-encapsulated spike mRNA elicits 4.7-fold higher IgG titers and robust CD8+ T-cell responses (characterized by IFN-γ+, TNF-α+, and granzyme B+ markers) compared to SM-102/ALC-0315 LNPs. Notably, AA2 exhibits minimal off-target accumulation, with low biodistribution in the liver and spleen. Its slightly positive surface charge (+3–5 mV) enhances cellular uptake, while the biodegradable ester structure ensures metabolic clearance, reducing potential toxicity.

The AA15 lipid, an amino acid-derived ionizable lipid, integrates a carboxylic acid-containing headgroup and biodegradable branched ester tails (R2) to enhance mRNA delivery. Optimized as AA15V LNP, it exhibits a hydrodynamic diameter of 102.3 ± 4.1 nm, low polydispersity (PDI <0.15), and slightly positive zeta potential (+4–6 mV), enabling efficient tumor-targeted delivery. With a pKa ~6.1–6.4, AA15V ensures protonation in acidic endosomes, promoting mRNA release. It achieves >85% mRNA encapsulation efficiency, critical for stable saRNA delivery. In vitro, AA15V LNP-sSE-SCTs induced sustained SE-SCT expression (69% H-2Kb+β2m+ B16F10 cells at 72 h), outperforming mRNA formulations. In vivo, a single intratumoral dose of AA15V LNP-sSE-SCTs suppressed tumor growth by 22-fold in vaccinated mice, synergizing with checkpoint inhibitors (anti-PD-1/CTLA-4) for complete regression in 28.6% of lymphoma models. Ex vivo, AA15V enabled SE-SCT expression in human glioblastoma (7.1% CD45− cells) and lung cancer samples (5.8–8.7%), underscoring clinical potential. Key data: pKa ~6.3; encapsulation: 85–89%; zeta: +4–6 mV; size: 102.3 ± 4.1 nm.

9C-SCC-10 is a biodegradable ionizable lipid with a nine-membered triaza crown-like headgroup and three disulfide-containing hydrophobic arms. In the cited mouse study, LNPs containing uncomplexed 9C-SCC-10 showed liver-biased mRNA-derived expression and an apparent LNP pKa of 6.42. Coordination with zinc produced the distinct Zn-9C-SCC-10 system, which shifted expression toward the lung. DC67451 refers to the uncomplexed lipid; the zinc-coordinated formulation is described separately in the literature analysis.

PPz-2R1 is an ionizable cationic lipid engineered for mRNA delivery via lipid nanoparticles (LNPs). These LNPs demonstrate remarkable lung-selective accumulation in mice, showing significantly higher uptake compared to heart, liver, spleen, and kidney tissues. When loaded with PTEN mRNA, PPz-2R1 LNPs effectively restore tumor suppressor function in PTEN-deficient lung cancer cells and inhibit tumor progression in orthotopic models, with enhanced efficacy observed in combination with PD-1 blockade therapy.

Lipid 114 (pKa ~6.8) is an ionizable cationic lipid optimized for siRNA delivery via LNPs, demonstrating predominant hepatic accumulation with secondary renal uptake in murine models. When formulated with IL-1β-targeting siRNA, these LNPs effectively suppress pro-inflammatory cytokine expression in both macrophage cell lines and primary cells in a dose-dependent manner. In LPS/galactosamine-induced acute liver failure models, the therapeutic LNPs significantly reduce IL-1β levels in target organs while attenuating hepatic inflammation and injury markers.

BCP-NC2-C12 is an ionizable cationic lipid designed for mRNA delivery, forming LNPs that predominantly localize to hepatic and splenic tissues in vivo. When formulated with CRISPR-Cas9 components (Cas9 mRNA and Pcsk9-targeting sgRNA), these LNPs effectively generate gene-editing indels and significantly lower circulating PCSK9 levels in murine models.

Lipid U 105 is an ionizable cationic lipid (pKa 6.65) specifically designed for circular RNA delivery via LNPs. These formulations effectively enhance VEGF-A expression in HUVECs, promoting endothelial cell proliferation and migration. When applied topically in diabetic mouse models, the VEGF-A-encoding circular RNA LNPs significantly accelerate wound healing, demonstrating therapeutic potential for impaired tissue repair.

Lipid A represents a modified variant of ALC-0315, functioning as an ionizable cationic lipid with a pKa of 4.67 for optimized nucleic acid delivery applications.

Derived from the natural amino acid homocysteine, CP-LC-1422 is an ionizable cationic lipid that enables robust in vivo delivery of various RNA forms (mRNA, cRNA, and saRNA), driving high protein expression. When formulated into LNPs (50/38.5/10/1.5 molar ratio of ionizable lipid/cholesterol/DOPE/PEG-lipid), it achieves superior spleen-specific targeting compared to commercial options through intravenous administration, while maintaining an excellent safety profile.

2N12B is a redox-responsive cationic lipid (pKa = 6.5) designed for siRNA delivery. Its LNPs mediate robust VEGFA knockdown in both cultured retinal cells and ex vivo mouse retina, while functionally impairing HUVEC motility. When administered in retinopathy models, the nanoparticles alleviate disease hallmarks including abnormal vessel growth and retinal vascular leakage.

Derived from the natural amino acid homocysteine, CP-LC-1428 is an ionizable cationic lipid that enables highly efficient in vivo delivery of multiple RNA formats (including mRNA, cRNA and saRNA) with robust protein expression. When formulated into standard LNPs (50:38.5:10:1.5 molar ratio of ionizable lipid:cholesterol:DOPE:PEG-lipid), it demonstrates superior spleen-selective targeting compared to conventional delivery systems following intravenous administration, while maintaining an excellent safety profile.

CP-LC-1074 is a homocysteine-derived ionizable cationic lipid that enables highly efficient in vivo delivery of various RNA therapeutics (including mRNA, cRNA, and saRNA) with robust protein expression. When formulated in standard LNP compositions (50:38.5:10:1.5 molar ratio of ionizable lipid:cholesterol:DOPE:PEG-lipid), it demonstrates superior lung-specific targeting compared to commercial alternatives following intravenous administration, while maintaining an excellent safety profile.

CP-LC-1447 is listed as a ionizable lipid for laboratory research use.

CP-LC-1073 is listed as a ionizable lipid for laboratory research use.

DSPE-polysarcosine100 represents an innovative amphiphilic conjugate, combining the phospholipid DSPE with a 100-unit polysarcosine chain terminated by an amine group. This polymer-modified lipid serves as a promising alternative to PEGylated compounds in nanoparticle formulations, offering reduced immunogenicity for both protein therapeutics and lipid-based delivery systems.

Hexa lipid 114 represents a structural derivative of lipid 114, engineered as an ionizable cationic compound for enhanced nucleic acid delivery applications.

HTO12 is an ionizable cationic lipid (pKa ~6.43) specifically designed for mRNA encapsulation in lipid nanoparticles. When formulated with complementary lipids, it enables efficient nucleic acid delivery in both cellular systems and living organisms.

FTT5 LLNs is a modified TT3-derived lipidoid optimized for nucleic acid delivery via lipid-like nanoparticles (LLNs). These formulations demonstrate hepatic tropism in mice and enhance reporter gene expression in Hep3B cells. Therapeutically, FTT5 LLNs successfully deliver Factor VIII mRNA to restore clotting activity in hemophilic mice and enable in vivo genome editing applications.

CAP 2 is a unique ionizable lipid featuring a bicholesterol structure connected by a phosphate linker with an amino terminus. This design enables efficient in vivo delivery of both mRNA and saRNA via LNPs. In a Dmc1-deficient mouse model of male infertility, saRNA-encoded Dmc1 delivered by CAP 2 LNPs demonstrated prolonged protein expression in testicular tissue compared to mRNA formulations. The treatment restored spermatogenesis, improving germ cell maturation, seminiferous tubule morphology, and ultimately yielding functional sperm capable of fertilization.

Lipid C-1 is an ionizable cationic amino lipid structurally derived from SM-102, optimized for enhanced mRNA delivery. When formulated into LNPs, it demonstrates superior transfection efficiency in Calu-3 cells, driving significantly higher luciferase reporter expression compared to its parent compound.

Lipid VII is a novel ionizable cationic lipid developed by Sanofi.Lipid VII demonstrates exceptional performance as a lipid nanoparticle delivery system, combining high efficiency with outstanding safety. Cellular assays reveal VII achieves 180,000 RLU transfection efficiency under serum conditions, surpassing traditional SS-OP systems by 2.25-fold while maintaining perfect 100% cellular viability and eliminating cytotoxicity risks that plague alternatives. In vivo systemic delivery shows rapid whole-body biodistribution, reaching photon emission levels exceeding 1.00E+10 photons/sec within 48 hours. VII exhibits superior organ targeting with a liver-specific accumulation ratio of 9.0, outperforming SS-OP systems by 50%, while reducing off-target spleen accumulation by 20%. Its versatility is further validated in therapeutic protein expression, where structural analogs achieve erythropoietin concentrations of 14 ng/mL, exceeding industry standards by 180%. For vaccine applications, VII generates a median HAI titer of 7,611 against H1N1 influenza—540 times higher than baseline buffers and more than double the next-best formulation. This evidence establishes VII as a breakthrough technology, offering unmatched efficiency, precision targeting, and clinical-grade safety across diverse applications.

A1-28 is a redox-responsive ionizable lipid featuring a disulfide linkage, designed for CRISPR component delivery. Its LNP formulations effectively package both Cas9 mRNA and sgRNA, enabling efficient genome editing in cultured cells.

ALC-0315 N-oxide represents a potential oxidative degradation product that may be present in formulated batches of the cationic lipid ALC-0315.

Westgene lipid 8 is a cationic lipid featuring a tertiary amine core with three alkyl chains (C1-C15) and two unsaturated C18 linoleate-like tails. Its ionizable amine enables pH-dependent charge for mRNA encapsulation in LNPs. Key structural elements include branched alkyl groups (X1/X2: C4, X3: C2) and ester-linked unsaturated R1/R2 chains, enhancing membrane fusion and endosomal escape. N Used in lipid nanoparticles (LNPs) with DOPE, cholesterol, and PEG-DMG, it demonstrates low cytotoxicity, high mRNA delivery efficiency, and spleen-targeted immune activation, making it suitable for vaccine/therapeutic delivery.

SL02 is a next-generation ionizable lipid featuring a unique branched hydrophobic domain and a pH-sensitive dimethylaminoethyl headgroup（pKa 6.25）developed by Seqirus. Its asymmetric lipid tails, combining unsaturated and saturated chains, enhance LNP fusogenicity and endosomal membrane disruption. With a slightly lower pKa than SL01, SL02 achieves efficient mRNA binding at acidic pH while maintaining neutral charge in circulation, reducing nonspecific interactions. In vitro, SL02-LNPs show superior transfection potency in BHK-V cells, attributed to improved cellular uptake and endosomal escape kinetics. In vivo, it elicits high neutralizing antibody titers (comparable to MF59-adjuvanted vaccines) and robust CD8+ T-cell activation. The lipid’s ester-based design ensures biodegradability, while PEGylation compatibility enhances colloidal stability. SL02’s tailored balance of hydrophobicity and ionization enables precise control over nanoparticle size (70–120 nm) and low polydispersity, positioning it as a leading candidate for saRNA-based vaccines and gene therapies.

SL01 is an ionizable cationic lipid compound pKa 6.31）developed by Seqirus, characterized by a biodegradable ester backbone and tertiary amine headgroup, enabling pH-dependent charge modulation. Its structure incorporates twin hydrophobic tails with unsaturated carbon chains, enhancing membrane fluidity and promoting endosomal escape. The lipid’s pKa (~6.5–7.0) optimizes nucleic acid complexation at physiological pH while minimizing cytotoxicity. SL01 demonstrates robust mRNA encapsulation efficiency (~90%) in lipid nanoparticles (LNPs) and facilitates intracellular delivery via endocytosis. Preclinical studies highlight its efficacy in inducing potent humoral and cellular immune responses, particularly in influenza mRNA vaccines. Its ester linkages ensure gradual metabolic clearance, reducing long-term toxicity. SL01-based LNPs exhibit stability in serum and compatibility with scalable manufacturing processes, making it a versatile candidate for therapeutic mRNA delivery.

​​nor-MC3​​ is a novel ionizable lipid develoed by Nanovation, derived from the MC3 structural framework, characterized by two ​​C17 alkyl chains​​ (each containing two Z-geometry double bonds) conjugated to a ​​4-(dimethylamino)butanoate​​ headgroup. Synthesized via a streamlined route involving Claisen condensation of methyl linoleate, hydrolysis/decarboxylation to generate a C17 ketone, reduction to the corresponding alcohol, and final esterification with 4-(dimethylamino)butanoic acid, nor-MC3 retains the ionizable amine functionality critical for pH-dependent nucleic acid binding and endosomal escape. Compared to the benchmark lipid MC3 (C18 chains), nor-MC3 demonstrates ​​superior mRNA delivery efficiency​​ in vitro (2-fold higher luciferase expression at 10 μg/mL mRNA) and enhanced in vivo biodistribution (higher liver and spleen targeting in mice). Notably, its shortened C17 chains challenge conventional assumptions about optimal hydrophobic chain length, offering improved synthetic scalability while maintaining or exceeding MC3's encapsulation efficiency (~95%), nanoparticle size (~80 nm), and low polydispersity (PDI ~0.08). For siRNA delivery, nor-MC3 achieves comparable EC₅₀ values (0.1644 μg/mL vs. MC3’s 0.1308 μg/mL), highlighting its versatility as a next-generation lipid nanoparticle (LNP) component for nucleic acid therapeutics.

ATX-129 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

ATX-111 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

ATX-132 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

ATX-100 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

ATX-106 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

Yoltech lipid 4​​, a highly efficient ionizable lipid disclosed in patent PCT/CN2023/116607, features a central tertiary amine group flanked by hydrophobic tails—specifically, a bis(2-ethylhexyl) core and a linoleyl (C18:2) chain linked via ester bonds. This structure enables pH-responsive behavior critical for mRNA/LNP delivery: neutral in circulation (reducing toxicity) but protonated in endosomes to facilitate membrane disruption and payload release. In murine studies targeting liver PCSK9, Compound 4 achieved ​​~90% gene-editing efficiency​​. Its optimized formulation yields LNPs of ​​70–150 nm​​ with >​​90% encapsulation​​, ideal for hepatocyte-specific delivery.

L2 is a redox-responsive lipid engineered for ​​ultra-potent siRNA delivery​​. With shorter hexyl (C6) tails and a carbamate linker, it demonstrates the ​​fastest biodegradation​​ (liver half-life: 2.6 days) among tested lipids. L2 achieves >80% FVII gene knockdown at just 0.01 mg/kg—surpassing both L1 and MC3 in siRNA potency. Its higher apparent pKa (6.90) enhances endosomal disruption, correlating with strong in vitro hEPO expression. While slightly less effective for mRNA than L1, L2’s unmatched siRNA silencing efficiency, rapid cytosolic self-immolation, and low cytotoxicity position it as a leading candidate for RNAi therapeutics targeting hepatic diseases.

HCQ-4​​ is a rationally engineered ionizable lipid derived from hydroxychloroquine (HCQ), featuring a ​​ditetradecylamine-derived twin-C14 saturated hydrocarbon tail​​ linked to the HCQ headgroup via a ​​succinic acid spacer​​. Synthesized through a three-step route involving HCQ deprotonation, ditetradecylamine carboxylation, and EDC/DMAP-mediated amidation, this lipid forms the core of optimized lipid nanoparticles (LNPs) at a molar ratio of ​​60:10:40:0.5 (HCQ-4:DOPE:cholesterol:DMG PEG 2000 )​​. The structure enables dual functionality: (1) ​​Spleen-selective mRNA delivery​​ (2.3-fold higher splenic vs. hepatic transfection) via 80-100 nm particle size, near-neutral charge (-3 mV), and low PEG density, facilitating immune cell uptake; (2) ​​Tumor microenvironment modulation​​ through HCQ-mediated repolarization of M2 macrophages to antitumor M1 phenotype (iNOS + cells ↑2.5-fold, CD206 + cells ↓60%). This bifunctional design synergistically enhances mRNA cancer vaccine efficacy, demonstrating superior prophylactic/therapeutic antitumor activity and antimetastatic effects compared to clinical benchmarks like MC-3 LNP.

ORNA lipid 144​​ is a novel ionizable lipid engineered for splenic RNA delivery developed by ORNA Therapeutics, featuring a biodegradable structure with a protonatable tertiary amine headgroup and ester-linked branched C14 alkyl chains. This design enables exceptional spleen-targeting capability, demonstrated by 3-fold higher luciferase expression in the spleen compared to benchmark lipids and near-complete B-cell depletion when delivering anti-CD19 CAR circRNA. It forms highly stable lipid nanoparticles maintaining homogeneous size (60–80 nm) and low polydispersity across diverse manufacturing conditions and buffer systems. Rapid clearance from the liver and spleen minimizes off-target accumulation, while high circRNA encapsulation efficiency (>90%) and pH-dependent endosomal escape make it ideal for immunotherapies and vaccines requiring precise splenic bioavailability and sustained efficacy.

CDL9​​ is an original cyclic disulfide lipid first designed, synthesized, and functionally validated in the study "In Vivo Demonstration of Enhanced mRNA Delivery by Cyclic Disulfide-Containing Lipid Nanoparticles for Facilitating Endosomal Escape" published in ​​RSC Medicinal Chemistry​​ (DOI: 10.1039/D5MD00084J).Its molecular architecture—featuring a ​​C18:2 di-unsaturated alkyl chain​​ linked to a tertiary amine headgroup modified with an α-lipoic acid-derived cyclic disulfide unit—was explicitly detailed in the paper's lipid library. Experimental data from this study demonstrated CDL9’s capacity to boost mRNA delivery efficiency by 6-fold in vitro and 5-fold in vivo when integrated into SM102-based LNPs, leveraging thiol-disulfide exchange for enhanced endosomal escape.

MeTis Lipid 5 is an ​​ionizable lipid​​ featuring a ​​pyrazole-based headgroup​​ and biodegradable ​​C8-ester twin tails​​ developed by MeTis Pharmaceuticals​​ (Patent CN118290339B)​​. It demonstrated ​​breakthrough in vivo efficacy​​ (7.08E+10 photons, luciferase assay), ​​surpassing MC3 lipid by 8.8-fold​​ in systemic mRNA delivery. The molecule achieves optimal ​​safety-profile​​ (96.4% cell viability) and ​​encapsulation efficiency​​ (96.4%), forming LNPs of ​​108.9 nm (PDI 0.17)​​ at N/P 6. Its ester-enabled rapid metabolization and balanced hydrophobicity position lipid 5 as a candidate for next-gen mRNA therapeutics.

MeTis Lipid 1 is an ionizable lipid featuring a pentacyclic core with geminal dimethyl groups and symmetrical C9 alkyl chains developed by Metis Pharm. According to Patent WO 2025/140421 A1, Lipid 1 demonstrated exceptional biological performance including: the highest SARS-CoV-2 neutralization titer (NT50 1:2146, 5.7-fold higher than ALC0315), potent humoral immunity with COVID-19 IgG titers reaching 1:1,000,000 post-boost and exclusive validation for VZV-gE IgG (1:1,000,000), favorable biophysical properties (124.5 nm LNP diameter, 0.2 PDI, 85% encapsulation efficiency), and excellent safety profile (hERG IC₅₀ >30 μM, Mini-Ames negative), establishing it as the lead compound in nucleic acid vaccine delivery.

Tidal Lipid 40is an ionizable cationic lipid engineered to deliver RNA with high precision to immune cells like macrophages. Based on ​​Tidal Therapeutics' patent US 20250205169A1​​, ​​ Its pH-responsive design shifts from a ​​+8 mV charge at pH 5.5​​ (enabling endosomal escape) to ​​near-neutral at pH 7.4​​ (reducing off -target binding), ensuring efficient intracellular release while maintaining blood stability. In lipid nanoparticles, Lipid 40 achieves ​​65% transfection efficiency in human macrophages​​—surpassing benchmarks like ALC-0315—and protects >95% of RNA payloads from degradation. Critically, it maintains particle integrity after freeze-thaw cycles with minimal size drift (<5 nm) and excels in in vivo targeting, driving potent gene expression in tumor-associated macrophages while avoiding liver/spleen accumulation. This combination of ​​precision delivery, stability, and low toxicity​​ makes it ideal for immunotherapies, such as reprogramming M2 macrophages to anti-tumor M1 states.

IAJD 294 is a ​​single-component ionizable amphiphilic Janus dendrimer​​ that autonomously coassembles with mRNA via simple injection into uniform monodisperse dendrimersome nanoparticles (DNPs, 85 nm diameter, PDI<0.2), eliminating complex multi-component formulations. Its optimized ​​3,5-benzoyl ester linkage​​ and symmetric hydrophobic tails enable ​​dual-organ targeting​​: ​Spleen​​: 2.97 × 10⁷ RLU (50% of total activity) ​​Lymph nodes​​: 10⁶ RLU (10× higher than IAJD 87) through ​​partial hydrophobic interdigitation​​ (stabilizing DNPs for enhanced lymphatic uptake) and ​​pKa ~6.5​​ (facilitating endosomal escape), validating constitutional isomerism for precision delivery.

SAL12 is a novel ionizable lipid derivative that integrates a non-nucleotide STING agonist (agonist 6) with an amino lipid tail through an ester bond, forming the core component of specialized lipid nanoparticles (SAL12-LNPs). These nanoparticles are designed for dual functionality: they efficiently encapsulate and deliver mRNA into dendritic cells while concurrently activating the STING pathway to stimulate innate immunity.

GVS-18-B34 is a highly potent, silicon ether-based ionizable lipid that enables efficient mRNA delivery via lipid nanoparticles (LNPs). Its key advantage lies in a biodegradable silyl ether linkage, which undergoes rapid, non-enzymatic hydrolysis, leading to near-complete clearance from the liver within 24 hours in both mice and non-human primates (NHPs). This degradation mechanism is species-agnostic, overcoming the variability associated with esterase-dependent lipids. In vivo, GVS-18-B34 LNPs demonstrated superior liver-specific protein expression and a high liver-to-spleen signal ratio, indicating minimal off-target accumulation and reduced immune stimulation compared to benchmarks like MC3 and SM-102. The LNPs exhibited excellent stability when stored frozen at -80°C, maintaining integrity over multiple freeze-thaw cycles. With its optimal pKa (~6.3) and efficient endosomal escape profile, GVS-18-B34 represents a promising candidate for therapeutic applications requiring frequent dosing, combining high potency with a favorable safety profile derived from its rapid clearance.

iChol15-C4A2 is a groundbreaking ionizable cholesteryl lipid, expertly designed to overcome the primary challenge of liver-centric accumulation in mRNA therapeutics. Its innovative "two-in-one" structure seamlessly integrates cholesterol with an ionizable headgroup, enabling the formation of stable, three-component Lipid Nanoparticles (Tc-LNPs).The key advantage of Tc-LNPs formulated with iChol15-CA2 is their significantly reduced adsorption of Apolipoprotein E (ApoE).This unique property directly attenuates ApoE/LDLR-mediated uptake by liver cells, dramatically shifting biodistribution toward extrahepatic tissues. Peer-validated research demonstrates a remarkable 20-50 fold increase in the spleen-to-liver mRNA expression ratio compared to standard LNPs like ALC-0315, unlocking unparalleled potential for targeting the immune system. Beyond its superior targeting capability, iChol15-C4A2 ensures high mRNA encapsulation efficiency, excellent colloidal stability, and proven biocompatibility. It offers a powerful, off-the-shelf solution to advance next-generation mRNA applications, from innovative vaccines and cancer immunotherapies to treatments for splenic disorders. Discover how iChol15-C4A2 can transform your delivery platform.

GVS-18-B35 is a leading silicon ether-based ionizable lipid that demonstrates exceptional performance in mRNA delivery. It features a biodegradable silyl ether linkage, which undergoes rapid, non-enzymatic hydrolysis, enabling near-complete clearance from the liver within 24 hours in both mice and non-human primates (NHPs). This degradation mechanism is independent of variable enzymatic activity, ensuring consistent pharmacokinetics across species. In vivo, GVS-18-B35 lipid nanoparticles (LNPs) achieve superior liver-specific protein expression with minimal off-target accumulation in the spleen, resulting in a high liver-to-spleen signal ratio and reduced immune stimulation. The LNPs exhibit excellent stability under frozen storage (-80°C) and maintain critical quality attributes, including particle size, polydispersity, and encapsulation efficiency, through multiple freeze-thaw cycles. With an optimal pKa (~6.3) and enhanced endosomal escape capability, GVS-18-B35 represents a robust and versatile platform for mRNA therapeutics, particularly suited for applications requiring frequent dosing due to its unique combination of high potency and rapid clearance profile.

GL5 is an ionizable guanidine-based lipid nanoparticle (G-LNP) designed for superior mRNA delivery. Its guanidinocarbonyl-pyrrole (GCP) headgroup enables pH-responsive behavior and strong mRNA binding via bidentate hydrogen bonds. The cholesterol-free GL5-3 formulation forms compact, stable nanoparticles (~90-120 nm) that exhibit excellent spleen-targeting capability after intravenous injection.GL5-LNPs efficiently deliver mRNA to antigen-presenting cells (APCs), enhancing antigen presentation and T cell activation. In cancer immunotherapy models, GL5-based mRNA vaccines provided complete tumor protection and induced durable immune memory. The platform also enables mRNA delivery to other organs like the pancreas via different administration routes, demonstrating remarkable versatility and therapeutic potential.

(4S)-KEL12​​ is a novel, biodegradable ionizable lipid developed for advanced mRNA vaccine delivery. It was rationally designed by incorporating both a ketal group in the linker and ester segments in the hydrophobic tails, a dual-degradable strategy aimed at enhancing its safety profile. Through iterative optimization, (4S)-KEL12 was identified as a lead candidate with an optimal pKa value of approximately 6.78, which is crucial for efficient mRNA encapsulation and endosomal release.

Based on the data from patent US 20250127728A1, CICL-238​ emerges as a highly promising ionizable lipid candidate, demonstrating notable advantages for targeted delivery applications. It achieves exceptional transfection efficiency—reaching approximately 90% of CICL-207's performance in splenic T-cells even at a reduced lipid ratio of 50% in LNP formulations. Additionally, CICL-238 exhibits minimal off-target expression​ in hepatocytes (<8%, comparable to CICL-207), underscoring its enhanced specificity for immune cells over liver tissues. Its optimized structure likely contributes to efficient endosomal escape and reduced Kupffer cell uptake, making it ideal for liver-related therapies​ (e.g., siRNA silencing for metabolic diseases) and potentially broadening applications to genetic medicine where precision and safety are paramount. Further validation in disease models could solidify its role as a versatile, low-toxicity alternative to benchmark lipids.

ATX-012 is an ionizable cationic lipid specifically designed for mRNA delivery systems. Its unique chemical structure enables key functions in lipid nanoparticle (LNP) formulations, such as facilitating mRNA encapsulation and enhancing endosomal escape for efficient intracellular delivery.

CLinDMA, a cationic lipid known to potentially trigger inflammatory responses, is utilized in the synthesis of LNP201. This liposome-based assembly is specifically designed for the systemic delivery of siRNA.

14:0 DAP (1,2-dimyristoyl-3-dimethylammonium-propane ) is a cationic lipid that can be used for drug delivery.

Fluorescent DOTAP, a cationic lipid, can be used for the research of nucleic acid and protein delivery.

Transfectam is a cationic lipid able to interact with DNA to form complexes that mediate efficient gene transfer into various eukaryotic cells.

mono-Pal-MTO is a palm oil-based lipid produced by combining the anticancer drug mitoxantrone (MTO) with palmitoleic acid. When nanoparticles of mono-Pal-MTO and di-Pal-MTO are combined in a molar ratio of 1:1, they show effective siRNA cell delivery and enhance anticancer activity.

di-Pal-MTO is a palm oil-based lipid produced by combining the anticancer drug mitoxantrone (MTO) with palmitoleic acid. When nanoparticles of mono-Pal-MTO and di-Pal-MTO are combined in a molar ratio of 1:1, they show effective siRNA cell delivery and enhance anticancer activity.

PL1 is a novel biomimetic phospholipid.

Lipid A1-D1-5 is an ionizable lipid-like substance used for RNA interference therapy in heat-stable ionizable lipid-like nanoparticles (iLAND) for the treatment of hyperlipidemia.

DMAP-BLP is a lipid for RNA and vaccine delivery.DMAP-BLP exhibits optimized bilayer destabilizing and pKa properties leading to highly potent gene silencing in hepatocytes following IV administration that is similar to “gold standard” lipids such as DLinMC3-DMA.

ATX-081 is listed as a ionizable lipid for laboratory research use.

ATX-083 is listed as a ionizable lipid for laboratory research use.

ATX-084 is listed as a ionizable lipid for laboratory research use.

ATX-087 is listed as a ionizable lipid for laboratory research use.

Lipid 23 is an ionizable cationic amino lipid (pKa = 5.7) that has been used with other lipids in the formulation of lipid nanoparticles (LNPs). Intravenous administration of LNPs containing lipid 23 and encapsulating an mRNA reporter accumulate specifically in the mouse liver.

C12-113 is a novel polyamine-derived lipidoid for gene delivery.

Lipidoid XMaN6 is an ionizable lipid with universality was screened out from the adamantyl-based ionizable lipid series, which could functionally deliver highly diverse types of nucleic acids.

AO16 is a literature-reported antioxidant ionizable lipid derived from the SM-102 scaffold.

ATX-95 is an unsaturated ionizable lipid utilized in the formulation of lipid nanoparticles for drug delivery.