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

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

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

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.

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

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

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.

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

Galnac Lipid 29 is from Prime Medicine Patent: WO2024220807. Compound 29 is a GalNAc-functionalized lipid featuring a tripartite structure: an N-acetylgalactosamine (GalNAc) targeting moiety for ASGPR-mediated liver uptake, a flexible PEG-based linker (e.g., ethylene glycol repeats), and dual C18 alkyl chains for lipid nanoparticle (LNP) integration. Its design includes stereospecific amide/urethane bonds (R/S configurations) to optimize stability and ligand orientation. Preclinical data demonstrate enhanced prime editing efficiency (>2-fold vs controls) in hepatocytes at low doses, attributed to improved endosomal escape and payload release. The compound enables liver-specific delivery of CRISPR systems while minimizing off-target accumulation, with <5% activity in non-hepatic cells.

CVL1 (C24)​​ is an ionizable lipid developed by CureVac for mRNA delivery, featuring a vitamin E (α-tocopherol) core linked via a thioether bridge to piperidine-based cationic headgroups. Its unique design enables pH-dependent charge switching (neutral at physiological pH, cationic in endosomes) for efficient mRNA encapsulation and endosomal escape. Formulated in lipid nanoparticles (LNPs) with DPhyPS and PMOZ4, CVL1 preferentially targets spleen and lymph node dendritic cells (DCs), enhancing antigen presentation and T-cell immunity. Key advantages include high mRNA encapsulation (>90%), stability under lyophilization, and reduced liver accumulation compared to PEGylated LNPs. In preclinical studies, CVL1-based LNPs induced robust CD8+/CD4+ T-cell responses and IgG2a-dominant antibody titers against tumor antigens (e.g., Trp2). With a particle size of 70–120 nm and low polydispersity (PDI <0.2), CVL1 balances delivery efficiency and biocompatibility, making it ideal for cancer and infectious disease vaccines requiring strong cellular immunity. Its degradable ester and thioether bonds further improve safety profiles.

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

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

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

LNP Lipid-8 (11-A-M) is an ionizable lipid, which can be used for lipid nanoparticles (LNP) to deliver siRNA to T cells without targeting to ligands. LNP LIPs-8 loaded with GFP siRNA (siGFP), and significantly causes GFP gene silencing in mice model.

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

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

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.

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.

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

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.

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.

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

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

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

OF-Deg-Lin is a biodegradable lipid containing an ester group, developed from the nonbiodegradable, linoleic acid derived OF-02; mRNA-LNPs containing OF-Deg-Lin showed high expression in the spleen. The ionizable lipid Of-Deg-Lin was synthesized, which possessed the similar chemical structure with OF-02.Both Of-Deg-Lin and OF-02 had diketopiperazine core and doubly unsaturated tails, and the difference between them was that Of-02 contained nondegradable 1,2-amino-alcohol linkages, whereas Of-Deg-Lin contained degradable ester linkages The change of linker altered iLNPs distribution and mRNA expression in vivo. Although the Of-Deg-Lin iLNPs could accumulate in the liver and spleen, they induced the expression of most functional proteins in B lymphocytes of spleen (over 85% of the total protein), not in the liver. Of-Deg-Lin iLNPs can deliver mRNA and express functional proteins in the spleen specifically, but the mechanism is unclear.

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

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