Browse our lipid products for in vivo CAR research. Compare product names, catalog numbers and applications below, then open a product page for specifications, pricing and ordering.
Lipid 6 is a literature-reported ionizable lipid for ex vivo mRNA delivery to primary human T cells. In Gao et al. (2026), LNPs containing Lipid 6 generated MUC1-CAR T cells that were assessed against MUC1-positive cancer cell lines in vitro.
Lipid 43 is an ionizable lipid disclosed as Compound 43 in WO 2024/109794. In the patent's TMF30 formulation, mRNA-LNPs showed predominantly splenic reporter expression after administration in mice. Its structure, molecular formula, molecular weight and SMILES were assigned from the compound-specific synthesis scheme and checked against the reported proton count.
503O8,12 is a branched-tail ionizable lipidoid prepared from amine head 503 and saturated 2-octyldodecyl acrylate. In a four-component, DOPE-containing LNP, it produced predominantly splenic reporter expression after intravenous mRNA administration in mice. It is a research candidate for extrahepatic mRNA formulation screening; cell-specific spleen delivery and therapeutic efficacy were not established in this study.
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.
CL15F 7-5 is a piperidine-based ionizable lipid from the CL15F library, characterized by a symmetrically branched tail structure with a 7-carbon main chain and a 5-carbon side chain. This moderate tail length positions it between short-tail (e.g., CL15F 6-4) and long-tail (e.g., CL15F 14-12) variants, granting it a unique balance in mRNA delivery properties. Its LNPs exhibit optimized organ selectivity, enabling significant mRNA expression in both the spleen and muscle, as demonstrated by in vivo luciferase assays following intravenous and intramuscular administration. This lipid structure facilitates a favorable DSPC surface density on LNPs, which moderates interactions with serum proteins like ApoE, thereby reducing rapid hepatic clearance and promoting extrahepatic delivery. In vaccine applications, CL15F 7-5 LNPs encapsulating SARS-CoV-2 RBD mRNA elicited robust anti-RBD IgG titers and neutralizing antibodies in mice, outperforming the clinically benchmarked SM-102 lipid. The piperidine headgroup further contributes to storage stability by minimizing the generation of aldehyde impurities that can form mRNA-lipid adducts. Consequently, CL15F 7-5 represents a versatile lipid for developing stable, spleen-targeted mRNA vaccines and therapeutics, leveraging tail-length engineering for enhanced efficacy without complex formulation changes.
CICL 207 is structurally optimized based on Lipid CICL-1. CICL207 is a constrained ionizable cationic lipid designed for lipid nanoparticle (LNP) delivery systems developed by Capstan. Its structure features a rigid cyclic backbone (e.g., pyrrolidine-derived core) paired with a tertiary amine group that ionizes at acidic pH (pKa ~6.5–7.0), enhancing endosomal escape. The lipid includes asymmetric hydrophobic tails (likely C14–C18 alkyl/ester chains) to stabilize LNP membranes and improve nucleic acid encapsulation. Integrated into LNPs (e.g., 58% CICL-207, 10% DSPC, 30.5% cholesterol, PEG-lipids), it enables targeted delivery to T cells (anti-CD5/CD8 tLNPs) with high transfection efficiency (spleen T cells >70% mCherry+), reduced liver uptake, and low toxicity (no significant ALT/AST elevation in rats). Its constrained design balances stability, tissue specificity, and biocompatibility for gene therapy applications.CICL 207 (F50) significantly outperforms CICL-1 by delivering dramatically enhanced target cell transfection with reduced off-target effects. It achieves >50% transfection efficiency in splenic T-cells—nearly double that of CICL-1—while slashing off-target expression in liver cells to <5% (versus >15% for CICL-1. This precision translates to superior therapeutic outcomes: CICL-207 enables ~95% B-cell depletion in CAR-T applications, far exceeding CICL-1 ’s ~60% efficacy. Critically, it maintains an exceptional safety profile, showing no significant liver toxicity or inflammatory cytokine elevation even at high doses. Furthermore, CICL-207 demonstrates 2-fold higher transfection efficiency in hematopoietic stem cells, enabling robust gene editing. Its optimized pKa (~6.5) and constrained amine structure enhance endosomal escape while minimizing Kupffer cell uptake, making it ideal for targeted therapeutics requiring both potency and safety.
PL-40 is a cardiolipin-mimetic ionizable lipid engineered for high-efficiency, antibody-free mRNA delivery to T cells. PL 40 LNPs exhibit a mean particle size of 120 nm, zeta potential of -5.19 mV, and >80% mRNA encapsulation efficiency, with excellent plasma stability (≤5% size change after 6h in serum). Cryo-TEM reveals polyhedral nanoparticles with phase-separated domains, while SAXS confirms tight mRNA packing (d-spacing: ~3 nm vs. 6.64 nm in conventional LNPs). AFM demonstrates exceptional rigidity (high bending modulus), enabling T cell-selective uptake via actin-mediated endocytosis (>2× higher than ALC0315 LNPs).In primary human T cells, PL40 LNPs achieve >90% transfection at 0.5 μg mRNA dose and sustain >100× higher luciferase expression than benchmark lipids. When delivering circular RNA, they extend protein expression >5 days with superior spleen tropism (spleen:liver ratio = 2.63). Crucially, they reprogram T cells into functional CAR-Ts in vivo without antibody conjugation, evading exhaustion markers (no Tim-3/PD-1 upregulation). Therapeutically, PL40-based uPAR-targeted CAR mRNA reduces liver fibrosis (collagen↓50%, ALT↓50%) and rheumatoid arthritis severity (clinical scores↓60%) by clearing senescent cells. Humanized anti-uPAR CARs delivered via PL40 show near-complete cytotoxicity (>95%) against uPAR+ cells, underscoring clinical translatability.
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.
ILB-3132 (E12LA6B603) is an ionizable lipid for mRNA-LNP research. View product specifications, available pack sizes and supporting information.
PyCB lipid (MeDZ) is a rationally designed zwitterionic ionizable lipid that serves as a core functional component in the novel three-component (ThrCo) lipid nanoparticle (LNP) platform. It is synthesized by covalently attaching a zwitterionic PyCB structure to the hydroxyl group of the clinically available ionizable lipid ALC-0315.Its key feature is its pH-responsive behavior. At physiological pH (~7.4), the PyCB headgroup exhibits zwitterionic properties, forming charge-assisted hydrogen bonds with water molecules (PyCB-H₂O complexes). This confers high hydrophilicity to the LNP surface, enhancing stability in aqueous environments and reducing nonspecific protein adsorption in the bloodstream. This zwitterionic surface effectively mimics and replaces PEGylated lipids, thereby avoiding PEG immunogenicity and the associated Accelerated Blood Clearance (ABC) effect upon repeated administrations.Crucially, in the acidic environment of endosomes (pH ~6.5), the PyCB group undergoes strong protonation, rapidly transforming into a cationic state (PyCB-H₃O⁺ complexes). This promotes efficient fusion with and disruption of the endosomal membrane, facilitating the escape and cytoplasmic release of encapsulated mRNA.By replacing both cholesterol and PEGylated lipids in traditional LNPs, PyCB lipid enables the redirection of LNP biodistribution from the liver to the spleen, achieving superior spleen-specific mRNA translation and enhancing antigen presentation for potent immune activation.
AMG514 is a novel ionizable lipid designed for formulating spleen-targeting lipid nanoparticles (LNPs) to deliver immune‑remodeling mRNAs (IR‑mRNAs). Its key advantage lies in the formation of a unique “protein corona” enriched with vitronectin, coagulation factors, and specific apolipoproteins (e.g., ApoA‑IV), together with its relatively high apparent pKa (~7.5), which actively redirects LNPs to the spleen instead of the liver. This precise spleen‑targeting property enables efficient transfection of splenic antigen‑presenting cells (APCs). As a vaccine adjuvant, AMG514‑LNPs therefore elicit a more robust activation of adaptive immunity compared to conventional LNPs (e.g., cKK‑E12), generating significantly enhanced antigen‑specific CD8⁺ T‑cell and antibody responses, and inducing durable anti‑tumor immune memory in preclinical models.
C12-4 (Lipid A-4,Lipid F3) is a branched-chain ionizable cationic lipidoid that has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA. LNPs containing lipid A4 and encapsulating an mRNA reporter accumulate in the uterus, placenta, and ovaries, as well as to the spleen and liver, in pregnant mouse dams unlike LNPs containing the branched-chain ionizable cationic lipidoid C12-200, which primarily accumulate in the liver. Intravenous administration of LNPs containing lipid A4 and encapsulating mRNA encoding VEGF increase placental VEGFR1 levels and mean fetal blood vessel area without inducing liver damage in pregnant mouse dams.
An ionizable lipid studied in targeted LNPs for immune-cell mRNA delivery and in vivo CAR research.
A reference ionizable lipid for hepatic siRNA delivery and comparative mRNA-LNP research.
A degradable dendritic lipidoid reported for small-RNA delivery and subsequent mRNA-LNP research.
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).
An ionizable lipid studied for mRNA delivery to primary human T cells and ex vivo CAR-T engineering.
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.
76-O17Se is a selenium-containing lipidoid investigated for intracellular delivery of mRNA and genome-editing proteins. In CAR-T cell engineering studies, 76-O17Se-based lipid nanoparticles delivered N1-methylpseudouridine-modified anti-CD19 CAR mRNA into CD8+ T lymphocytes. The resulting CAR-T cells demonstrated cytotoxic activity against B-cell lymphoma cells in vitro, supporting its application in nonviral mRNA delivery and transient immune-cell engineering research.
9322-O16B is a lipidoid for the efficient delivery of antiCD19 mRNA CAR to murine primary macrophages. LNP 9322-O16B is more efficient than delivery with lipofectamine 2000 (LPF2K) or MC3.
Lipid C14-A1 is an ionizable lipid. C14-A1-LPN is a potent and safe LNP platform to deliver Foxp3 mRNA to CD4+ T cells to engineer immunosuppressive FP3T cells.
Lipid C12-A1 is an ionizable lipid. C12-A1-LPN is a potent and safe LNP platform to deliver Foxp3 mRNA to CD4+ T cells to engineer immunosuppressive FP3T cells. C12-A1 has a slightly lower average cell viability than C14-A1.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Trp-L1-T4 is a novel tryptophan-derived ionizable lipid that serves as the core functional component of the optimized lipid nanoparticle (TLNP/RLNP) platform. Its primary function is to enable the efficient encapsulation and in vivo delivery of self-amplifying RNA (saRNA) cargo. Specifically, it facilitates high transfection efficiency and cytosolic release of the RNA payload in target follicular helper T (Tfh) cells, with minimal cytotoxicity. This capability is crucial for reprogramming pathogenic Tfh cells into regulatory CAR-Tfh cells, forming the foundation of the study's therapeutic strategy.
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 an ionizable lipid for mRNA delivery research. View product specifications, available pack sizes and supporting information.
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.
A3B7C2 is an imidazole-containing ionizable lipid evaluated in a four-component LNP for spleen-selective reporter mRNA expression.
A1B7C2 is an imidazole‑based ionizable lipid from the IMIL library. It features dimethylamino‑propyl imidazole head group, paired with B7 hydrophobic tails and C2 degradable ester linkers. LNPs assembled from A1B7C2 can effectively accumulate within the spleen after systemic administration. It mediates mRNA expression in splenic tissue, and is applied as a key control compound to investigate structure‑activity relationships for spleen‑targeted nucleic acid delivery.
113-O12B LNP, an LN-targeting LNP delivery system, is developed for a mRNA cancer vaccine.
OF-C4-Deg-Lin is a novel ionizable lipid for RNA delivery.
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.
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.
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.
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.
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.
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.
YK-TLR-001 is a cyclic acetal-based ionizable lipid for mRNA delivery. YK-TLR-001 LNPs are demonstrated to enhance mRNA expression in the spleens and to induce exceptional maturation of antigen-presenting cells (APCs) and to promote antigen presentation.
2Ac3-C18 is a core-degradable ionizable lipid with two ester-linked branches, two tertiary amines and two C18 alkyl tails. Its four-component LNPs, formulated with DOPE, cholesterol and DMG-PEG2000, showed spleen-selective reporter-mRNA expression after intravenous administration in mice.
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.
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.
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.
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.
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.
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.
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.
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.
E8i-200 is a novel Branched Endosomal Disruptor (BEND) ionizable lipid, designed to enhance the efficiency of lipid nanoparticles (LNPs) in drug delivery, particularly for mRNA and protein delivery. Its unique structure, featuring terminal branching, improves endosomal escape, a critical step in the delivery of therapeutic cargo into cells.E8i-200 is designed to enhance endosomal escape, a key bottleneck in mRNA and protein delivery. Its terminal branching structure provides several advantages:Improved Endosomal Membrane Penetration: The branched structure allows E8i-200 to more effectively disrupt endosomal membranes, facilitating the release of mRNA and proteins into the cytoplasm.Enhanced Gene Editing Efficiency: E8i-200 has been shown to significantly improve the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes, enabling efficient gene editing in vivo.E8i-200 significantly enhanced mRNA expression in the liver, outperforming traditional linear lipids like C12-200 in mouse models.E8i-200 effectively delivered CRISPR-Cas9 RNP complexes, achieving high editing efficiency in the liver, surpassing that of linear lipids.E8i-200 also showed high transfection efficiency and low cytotoxicity in T cells, making it a promising candidate for CAR-T cell engineering and other immunotherapies.
C14-O2 is an oxidized lipid for mRNA delivery. C14-O2-LNP is capable of potent and selective delivery of mRNA to blood monocytes. C14-O2 LNP is used to deliver a functional CD19-CAR mRNA and is shown to engineer functional CAR monocytes directly in situ.
TE-EP8-S is a single-component, ionizable cationic lipid designed specifically for the targeted delivery of mRNA to T cells within the spleen. This innovative lipid formulation enhances the efficiency and precision of mRNA-based therapies by ensuring optimal cellular uptake and expression in immune cells. Its unique structure and properties make it a promising tool for advancing immunotherapeutic applications.
Si12-C10 is a siloxane-incorporated lipid for spleen-targeting mRNA delivery. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy.
Lipid I97 is a vitamin B5-derived ionizable lipid for mRNA vaccine delivery. Lipid I97 LNP specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies with low toxicity.
YHS-12 is an ionizable cationic lipid (pKa = 6.506) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA and mRNA in vitro and in vivo.1 LNPs containing YHS-12 and the macrophage targeting peptide CRVLRSGSC and encapsulating mRNA encoding chimeric antigen receptor targeting methicillin-resistant S. aureus (MRSA) and siRNA targeting caspase-11 increase the phagocytosis rate of MRSA in RAW 264.7 macrophages and primary mouse bone marrow-derived macrophages (BMDMs). Intravenous administration of these LNPs decreases blood bacterial burden and increases survival in a model of sepsis using cyclophosphamide-induced immunosuppressed mice.
Derived from the natural amino acid homocysteine, CP-LC-1422 is an ionizable cationic lipid that enables robust in vivo delivery of various RNA forms (mRNA, cRNA, and saRNA), driving high protein expression. When formulated into LNPs (50/38.5/10/1.5 molar ratio of ionizable lipid/cholesterol/DOPE/PEG-lipid), it achieves superior spleen-specific targeting compared to commercial options through intravenous administration, while maintaining an excellent safety profile.
Westgene lipid 8 is a cationic lipid featuring a tertiary amine core with three alkyl chains (C1-C15) and two unsaturated C18 linoleate-like tails. Its ionizable amine enables pH-dependent charge for mRNA encapsulation in LNPs. Key structural elements include branched alkyl groups (X1/X2: C4, X3: C2) and ester-linked unsaturated R1/R2 chains, enhancing membrane fusion and endosomal escape. N Used in lipid nanoparticles (LNPs) with DOPE, cholesterol, and PEG-DMG, it demonstrates low cytotoxicity, high mRNA delivery efficiency, and spleen-targeted immune activation, making it suitable for vaccine/therapeutic delivery.
HCQ-4 is a rationally engineered ionizable lipid derived from hydroxychloroquine (HCQ), featuring a ditetradecylamine-derived twin-C14 saturated hydrocarbon tail linked to the HCQ headgroup via a succinic acid spacer. Synthesized through a three-step route involving HCQ deprotonation, ditetradecylamine carboxylation, and EDC/DMAP-mediated amidation, this lipid forms the core of optimized lipid nanoparticles (LNPs) at a molar ratio of 60:10:40:0.5 (HCQ-4:DOPE:cholesterol:DMG PEG 2000 ). The structure enables dual functionality: (1) Spleen-selective mRNA delivery (2.3-fold higher splenic vs. hepatic transfection) via 80-100 nm particle size, near-neutral charge (-3 mV), and low PEG density, facilitating immune cell uptake; (2) Tumor microenvironment modulation through HCQ-mediated repolarization of M2 macrophages to antitumor M1 phenotype (iNOS + cells ↑2.5-fold, CD206 + cells ↓60%). This bifunctional design synergistically enhances mRNA cancer vaccine efficacy, demonstrating superior prophylactic/therapeutic antitumor activity and antimetastatic effects compared to clinical benchmarks like MC-3 LNP.
ORNA lipid 144 is a novel ionizable lipid engineered for splenic RNA delivery developed by ORNA Therapeutics, featuring a biodegradable structure with a protonatable tertiary amine headgroup and ester-linked branched C14 alkyl chains. This design enables exceptional spleen-targeting capability, demonstrated by 3-fold higher luciferase expression in the spleen compared to benchmark lipids and near-complete B-cell depletion when delivering anti-CD19 CAR circRNA. It forms highly stable lipid nanoparticles maintaining homogeneous size (60–80 nm) and low polydispersity across diverse manufacturing conditions and buffer systems. Rapid clearance from the liver and spleen minimizes off-target accumulation, while high circRNA encapsulation efficiency (>90%) and pH-dependent endosomal escape make it ideal for immunotherapies and vaccines requiring precise splenic bioavailability and sustained efficacy.
IAJD 294 is a single-component ionizable amphiphilic Janus dendrimer that autonomously coassembles with mRNA via simple injection into uniform monodisperse dendrimersome nanoparticles (DNPs, 85 nm diameter, PDI<0.2), eliminating complex multi-component formulations. Its optimized 3,5-benzoyl ester linkage and symmetric hydrophobic tails enable dual-organ targeting: Spleen: 2.97 × 10⁷ RLU (50% of total activity) Lymph nodes: 10⁶ RLU (10× higher than IAJD 87) through partial hydrophobic interdigitation (stabilizing DNPs for enhanced lymphatic uptake) and pKa ~6.5 (facilitating endosomal escape), validating constitutional isomerism for precision delivery.
iChol15-C4A2 is a groundbreaking ionizable cholesteryl lipid, expertly designed to overcome the primary challenge of liver-centric accumulation in mRNA therapeutics. Its innovative "two-in-one" structure seamlessly integrates cholesterol with an ionizable headgroup, enabling the formation of stable, three-component Lipid Nanoparticles (Tc-LNPs).The key advantage of Tc-LNPs formulated with iChol15-CA2 is their significantly reduced adsorption of Apolipoprotein E (ApoE).This unique property directly attenuates ApoE/LDLR-mediated uptake by liver cells, dramatically shifting biodistribution toward extrahepatic tissues. Peer-validated research demonstrates a remarkable 20-50 fold increase in the spleen-to-liver mRNA expression ratio compared to standard LNPs like ALC-0315, unlocking unparalleled potential for targeting the immune system. Beyond its superior targeting capability, iChol15-C4A2 ensures high mRNA encapsulation efficiency, excellent colloidal stability, and proven biocompatibility. It offers a powerful, off-the-shelf solution to advance next-generation mRNA applications, from innovative vaccines and cancer immunotherapies to treatments for splenic disorders. Discover how iChol15-C4A2 can transform your delivery platform.
GL5 is an ionizable guanidine-based lipid nanoparticle (G-LNP) designed for superior mRNA delivery. Its guanidinocarbonyl-pyrrole (GCP) headgroup enables pH-responsive behavior and strong mRNA binding via bidentate hydrogen bonds. The cholesterol-free GL5-3 formulation forms compact, stable nanoparticles (~90-120 nm) that exhibit excellent spleen-targeting capability after intravenous injection.GL5-LNPs efficiently deliver mRNA to antigen-presenting cells (APCs), enhancing antigen presentation and T cell activation. In cancer immunotherapy models, GL5-based mRNA vaccines provided complete tumor protection and induced durable immune memory. The platform also enables mRNA delivery to other organs like the pancreas via different administration routes, demonstrating remarkable versatility and therapeutic potential.
(4S)-KEL12 is a novel, biodegradable ionizable lipid developed for advanced mRNA vaccine delivery. It was rationally designed by incorporating both a ketal group in the linker and ester segments in the hydrophobic tails, a dual-degradable strategy aimed at enhancing its safety profile. Through iterative optimization, (4S)-KEL12 was identified as a lead candidate with an optimal pKa value of approximately 6.78, which is crucial for efficient mRNA encapsulation and endosomal release.
Based on the data from patent US 20250127728A1, CICL-238 emerges as a highly promising ionizable lipid candidate, demonstrating notable advantages for targeted delivery applications. It achieves exceptional transfection efficiency—reaching approximately 90% of CICL-207's performance in splenic T-cells even at a reduced lipid ratio of 50% in LNP formulations. Additionally, CICL-238 exhibits minimal off-target expression in hepatocytes (<8%, comparable to CICL-207), underscoring its enhanced specificity for immune cells over liver tissues. Its optimized structure likely contributes to efficient endosomal escape and reduced Kupffer cell uptake, making it ideal for liver-related therapies (e.g., siRNA silencing for metabolic diseases) and potentially broadening applications to genetic medicine where precision and safety are paramount. Further validation in disease models could solidify its role as a versatile, low-toxicity alternative to benchmark lipids.
