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.

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.

​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. 

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.

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.

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.

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.

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.

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.

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

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​​. 

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.

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 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.

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.

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.

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​​.

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.

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.

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 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.

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.

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.

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

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.

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.

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.

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.