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.

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.

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.

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.

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.

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.

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 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.

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.

Lipid-87​​ is an ionizable lipid developed by Generation Bio, characterized by its ​​tertiary amine group​​ for pH-dependent protonation and ​​dual C16/C17 aliphatic chains​​ that enhance hydrophobic stability.As the core component (47.5–57.5 mol%) of stealth lipid nanoparticles (LNPs), Lipid87 enables extended blood circulation (>24-hour half-life vs. 30 min for conventional LNPs) by synergizing with steric-stabilizing polymers (e.g., DSG-PEG₂₀₀₀-OMe), achieves >95% encapsulation efficiency for mRNA/ceDNA with low cytotoxicity (IC₅₀ >100 μM), and drives liver-specific targeting (>80% hepatocyte transfection at 0.5 mpk), effectively restoring 40% FIX activity in hemophilia B models for over 7 days.

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.

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.

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

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.

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.

PAANIB-1 is a brain-penetrant PAAN/MIF nuclease inhibitor that prevents neurodegeneration that prevents neurodegeneration induced by α-syn PFF, AAV-α-syn overexpression, or MPTP intoxication in vivo.

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.

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

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.

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.

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.

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.