Featured lipid products

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 an ionizable lipidoid synthesized via Michael addition, combining a hydrophilic amine headgroup ("503" series) with two hydrophobic branched acrylate tails (C8 and C12 chains, likely with unsaturated bonds). Its design emphasizes organ-specific delivery, exhibiting ​​spleen-tropic targeting​​ in vivo.

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 an ionizable cationic lipid (pKa = 6.22) that has been used in the generation of lipid nanoparticles (LNPs) for mRNA delivery in vivo.1 LNPs containing 11-10-8 and encapsulating mRNA encoding the Cas9 nuclease and small-guide RNA (sgRNA) targeting transthyretin (TTR), a thyroid hormone carrier protein, decrease serum levels of TTR in mice. LNPs containing 11-10-8 and encapsulating mRNA encoding human fibroblast growth factor 21 (hFGF21) increase serum levels of hFGF21, decrease body and liver weights, and reduce the liver steatosis score in a mouse model of obesity induced by a high-fat diet.

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.

MK16 is an MK-0752-derived ionizable lipid developed for blood-brain-barrier-crossing mRNA delivery in preclinical mouse models. In the cited MK16 BLNP formulation, the authors reported an apparent LNP pKa of 6.86, a particle diameter of 137.0 ± 4.1 nm, 84.8 ± 1.5% mRNA encapsulation, and brain FLuc expression 8.3-fold above an MC3 LNP comparator after intravenous administration. The study also reported mRNA expression in neurons, astrocytes, brain capillary endothelial cells and microglia, as well as proof-of-concept results in cocaine-conditioned-place-preference and orthotopic glioblastoma models. All formulation and performance information shown below is literature-derived study evidence, not a product specification or a guarantee of reproducible LNP performance.

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.

PL40 is a cardiolipin-mimic phosphoramide (CAMP) lipid developed for antibody-free, T-cell-favored mRNA delivery. The cited study reported approximately 100-fold higher luciferase expression than ALC-0315 LNP and MessengerMax in primary human T cells under a specific in vitro assay, more than 80% GFP-positive human T cells at tested doses of at least 0.5 micrograms per 100,000 cells, and spleen-favored expression after intravenous administration. PL40 LNPs carrying circular uPAR CAR mRNA were also evaluated in preclinical liver-fibrosis and collagen-induced-arthritis models. All formulation and performance information shown below is literature-derived study evidence, not a product specification or a guarantee of reproducible LNP performance.

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 spirocyclic diamine ionizable lipid developed for spleen-biased mRNA delivery. In the cited mouse experiments, AMG514 LNPs produced approximately four-fold higher splenic reporter expression than a cKK-E12 comparator, transfected splenic dendritic cells and macrophages, and were evaluated for co-delivery of antigen and immune-remodeling mRNAs. The authors associated its approximately 7.5 apparent LNP pKa and serum- or plasma-derived protein-corona profile with the observed biodistribution, but did not establish a single causal targeting mechanism. All formulation and performance information shown below is literature-derived study evidence, not a product specification or a guarantee of reproducible LNP performance.

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.

CICL-1, identified in the cited study as Lipid 829 (L829), is an ionizable lipid used in targeted lipid nanoparticles for in vivo delivery of CAR mRNA to T cells. CD8-targeted L829 tLNPs preferentially engineered CD8-positive T cells in the reported models, produced rapid B-cell depletion, and controlled a humanized leukemia xenograft. In cynomolgus monkeys, anti-CD20 CAR mRNA tLNPs produced deep peripheral and tissue B-cell depletion, followed by repopulation dominated by naïve B cells; the authors described this finding as suggestive of immune reset. The supplied main article does not include Supplementary Table S1, so the complete five-lipid composition and N/P ratio are not presented as verified formulation values. All performance statements below are literature-reported study results, not product specifications or guaranteed outcomes.

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, an endogenous chemical and a neurotransmitter-derived lipidoid (NT-lipidoid), is an effective carrier for enhanced brain delivery of several blood-brain barrier (BBB)-impermeable cargos. Doping NT1-O12B into BBB-impermeable lipid nanoparticles (LNPs) gives the LNPs the ability to cross the BBB. NT-lipidoids formulation not only facilitate cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination.

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 next-generation, biodegradable lipid nanoparticle (LNP) engineered for highly efficient and targeted siRNA delivery. Designed through rational structure-activity criteria—including optimal tail length (O13), tertiary amines, and a surface pKa ≥5.5—this single-component LNP achieves unparalleled gene silencing with an ultra-low EC50 of 0.01 mg/kg in preclinical models.503O13 outperforms non-degradable counterparts (e.g., C12-200) with improved toxicity profiles—no hepatic necrosis or pancreatic inflammation—while maintaining rapid blood clearance (t1/2: 6 min) and organ-specific accumulation (liver/spleen).

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 an ionizable amino lipid.1 It has been used in the generation of lipid nanoparticles (LNPs) and has a pKa value of 6.8. LNPs containing TCL053 and encapsulating mRNA encoding the Cas9 nuclease, in combination with LNPs containing TCL053 and encapsulating single-guide RNA (sgRNA) targeting the Rosa26 locus, have been used to induce CRISPR-mediated gene editing in the mouse gastrocnemius muscle.TCL053 is an ionizable lipid that has received FDA approval for preparing mRNA vaccines. It is a three-tailed ionizable lipid to overcome the disadvantage of nonrepeatable administration of AAV vectors. In addition, combined with limb perfusion administration, TCL053 iLNPs could transiently deliver CRISPR-Cas9 mRNA and sgRNA to multiple muscle tissues, reducing immunogenicity and increasing the safety of iLNPs. It is great progress for treating Duchenne muscular dystrophy and other diseases that require multiple doses.

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.

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 lipidoid for the efficient delivery of antiCD19 mRNA CAR to murine primary macrophages. 76-O17Se is more efficient than delivery with lipofectamine 2000 (LPF2K) or MC3

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 asymmetric Ugi-reaction-derived ionizable lipid selected for muscle-focused mRNA delivery. In the cited mouse study, its optimized LNP produced muscle expression comparable to an SM-102 benchmark after intramuscular administration while showing no measurable reporter expression in the examined off-target organs. The same formulation delivered Cre mRNA for localized muscle gene editing and was evaluated with model-antigen and cancer-vaccine mRNAs. All formulation and performance information shown below is literature-derived study evidence, not a product specification or a guarantee of reproducible LNP performance.

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 biodegradable silicon-ether ionizable lipid reported for liver-directed mRNA delivery. The literature-verified structure contains a dimethylamino headgroup connected through a four-carbon linker to a silicon center bearing three cis-4-decenyl ether chains. In the cited study, GVS-18-B6 LNPs showed high mRNA encapsulation, an apparent LNP pKa of 6.15, preferential hepatic expression after intravenous administration, rapid tissue clearance, and favorable tolerability in the reported mouse and nonhuman-primate experiments. All formulation and performance values shown below are literature-reported study results, not specifications or guaranteed performance of the supplied lipid.

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.

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 brain-targeting lipid nanoparticle (BLNP) engineered for efficient mRNA delivery to the central nervous system (CNS) via intrathecal injection. It incorporates a tryptamine-derived ionizable lipid headgroup, myristic acid hydrocarbon tails, and a biodegradable carbonate ester linker, enabling pH-dependent mRNA encapsulation (81.7% efficiency) and brain cell-specific targeting. With a hydrodynamic diameter of 107.5 nm, near-neutral pKa (7.30), and mild positive charge, TD 5 demonstrates superior CNS tropism through serotonin receptor (5-HT1A)-mediated endocytosis. In vitro, TD-5 achieved 80.8% GFP expression in SH-SY5Y neuronal cells, outperforming MC3 LNPs by 50-fold. Following intrathecal administration in mice, TD-5 mediated GFP expression in 29.6% of neurons and 38.1% of astrocytes brain-wide, with 10-fold higher CNS specificity than peripheral organs. Genome editing studies showed TD5-delivered Cas9/sgRNA induced tdTomato activation in ≈30% of neurons and 40% of astrocytes across key brain regions. Safety profiling revealed minimal systemic immune responses (lower IL-6, IL-12p40 vs MC3 LNPs), normal hepatic/renal biomarkers, and no histopathological toxicity. The optimized structure balances myristic chain hydrophobicity for membrane interaction, ionizable amines for mRNA complexation, and tryptamine-mediated targeting for enhanced CNS uptake, establishing TD5 as a promising platform for CNS gene therapies.

​​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.

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 an L-tryptophan-derived ionizable lipid selected as the core lipid in the study's TLNP platform for self-amplifying RNA delivery to follicular helper T cells. The base TLNP formulation produced 59.8% GFP-positive primary Tfh cells under the reported in vitro conditions. In targeted variants, the authors combined CXCR5-antibody functionalization, Tfh-restricted RNA translation and, for in vivo work, Tween-20 modification to generate regulatory CAR-Tfh cells and evaluate a preclinical autoimmune-hepatitis model. These outcomes depend on the complete formulation, targeting ligand, RNA design and study conditions. All formulation and performance information shown below is literature-derived evidence, not a product specification or a guarantee of reproducible LNP performance.

A10 (Compound 16) is a diketopiperazine‑based ionizable lipid disclosed in WO 2025/217298 A1 (PCT/US2025/023899) developed by NAVA Therapeutics that enables potent, cell‑selective in vivo delivery of mRNA and nucleic acids without targeting ligands. It forms stable, well‑tolerated lipid nanoparticles (LNPs) that preferentially transfect hematopoietic stem cells (HSCs), bone marrow progenitors, lung epithelium, endothelium, and immune cells while minimizing liver off‑target delivery. In both mice and non‑human primates, A10‑containing LNPs drive functional mRNA expression and gene editing in CD34⁺ HSCs at clinically relevant low doses (0.25–1.0 mg/kg), supporting in vivo HSC gene therapy without ex vivo manipulation.

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‑based ionizable lipid, featuring dimethylamino‑imidazole head group connected via ester‑type degradable C2‑linker to two C14 unsaturated aliphatic tails. It forms LNPs achieving 98 % splenic transfection proportion, potent for splenic dendritic cell‑targeted mRNA delivery, superior to MC3, SM102.

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.

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 apparent pKa (6.57) facilitates efficient endosomal escape without compromising safety: even at 5 mg/kg, L1 causes no significant body weight loss or sustained inflammation. 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 unique ionizable lipid with a distinct degradable core structure：featuring 2 acrylate units and 3 amine groups—linked to a C18 alkyl chain. Its LNPs (formulated with DOPE/cholesterol/DMG-PEG2000) exhibit spleen-specific mRNA delivery in vivo.

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.

XH-07 is an innovative ionizable cationic lipid that forms the backbone of the JCXH-211 lipid nanoparticle (LNP) delivery system. This complex is engineered to encapsulate and deliver self-replicating RNA (srRNA) encoding interleukin-12 (IL-12), a potent immunostimulatory cytokine. The LNP formulation featuring XH-07 exhibits optimal physicochemical properties, such as a mean particle size of approximately 82.12 nm with low polydispersity, and a near-neutral zeta potential around -3.181 mV, which facilitates stable circulation and efficient cellular uptake upon intravenous administration. Upon delivery, the srRNA leverages the host cell's machinery to produce sustained levels of IL-12p70, as demonstrated in B16F10 tumor-bearing mice, where a single dose led to peak cytokine production in sera and tumors. This induced IL-12 expression activates T cells and NK cells, generating a robust antitumor response. In murine models of melanoma and breast cancer, JCXH-211 monotherapy resulted in significant tumor regression and complete responses in some subjects, and it synergized with anti-PD-1 therapy to enhance efficacy. Importantly, the safety profile was acceptable, with transient liver enzyme elevations in mice that normalized quickly, and no significant adverse events in cynomolgus monkeys after repeated dosing, as evidenced by stable clinical observations and pathology tests. Thus, XH-07 is pivotal for enabling the safe and effective delivery of IL-12 encoding RNA, positioning JCXH-211 as a promising cancer immunotherapy.

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 S-lipid containing a tertiary amine, a carboxylic acid, two secondary alcohols and two branched ester-linked hydrophobic domains. The cited study formulated E20 into switchable nanoparticles (SNPs) for mRNA and plasmid-DNA delivery. Literature-reported E20 SNP data include an apparent pKa of 4.99 for becoming neutral, an N/P ratio of 4.1 in the reported four-component formulation, efficient hEPO mRNA expression after intravenous administration, low immunostimulatory activity in the reported models and activity in an intratracheal IL-22 mRNA acute-lung-injury study. All formulation and performance information shown below is literature-derived study evidence, not a product specification or a guarantee of reproducible LNP performance.

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.