Lipid 331 is a biodegradable cyclic ionizable lipid. LNPs containing Lipid 331 result in robust transfection in the nasal and lung tissues of mice and efficient transfection of lung epithelial cells and lung-resident APCs. Lipid 331 is a promising candidate for mRNA vaccine delivery, offering the potential for further enhancing the potency of mRNA vaccines.

HGT5001, disclosed in patent US 2026/0125339 A1 by Translate Bio (now part of Sanofi), is a novel ionizable cationic lipid optimized for mRNA delivery. It enables efficient LNP assembly, high mRNA encapsulation, potent endosomal escape, and exceptional in vivo protein expression, with demonstrated efficacy in therapeutic mRNA applications, low toxicity, and favorable biocompatibility, making it a leading candidate for advanced mRNA therapeutics.

AKG-UO-1 is a novel ionizable lipid. With excellent oxidative stability and efficient endosomal escape capability, it significantly improves mRNA delivery efficiency and vaccine stability, reduces degradation risks, making it an optimal component for lipid nanoparticles.

KC‑34 (SPC‑A9) is a stereopure diketopiperazine‑based ionizable lipid from WO 2025/217299 A1 (PCT/US2025/023900) developed by Georgia Tech Research Corporation and Nava Therapeutics. It forms stable, well‑tolerated lipid nanoparticles (LNPs) that enable safe and efficient mRNA delivery to the liver, spleen, lung, and bone marrow in mice.

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

Lipid 11 is the optimal ionizable lipid disclosed by Liberate Bio, Inc. in patent WO2025/250730 A1, which can significantly improve the delivery efficiency of nucleic acid drugs to extrahepatic tissues including bone marrow, spleen and muscle, with excellent in vivo stability and safety.

DEA‑14‑DAP is a novel ionizable cationic SORT lipid. As a key component for central nervous system targeting, it enables lipid nanoparticles (LNPs) to specifically target microglia, significantly improving the delivery efficiency and cellular selectivity of nucleic acid drugs in the brain.

LIPID168(pKa ~6.5) ​​ is an optimized ionizable lipid engineered for in vivo mRNA delivery to hematopoietic stem cells (HSCs) in bone marrow. Developed by ​​Yoltech Therapeutics​​ through high-throughput screening of lipid libraries, it features a ​​diethylamino head group​​ and a tailored hydrophobic tail structure that enables antibody-free targeting. When Lipid 168 was formulated into lipid nanoparticles (LNPs), it achieved ​​48.5% base editing efficiency​​ in bone marrow cells —surpassing benchmarks like LIPID-028 (19.7%)—and reduced off-target liver editing from 71% to 19% by incorporating ​​miR-122 target sequences​​. In humanized β-thalassemia models, LNP 168 delivered ABE8e mRNA/sgRNA to patient-derived HSCs, yielding ​​42.6% editing at the HBG promoter​​, reactivating fetal hemoglobin (γ-globin) and rescuing erythroid defects . Its bone marrow specificity is driven by a unique ​​protein corona​​ enriched in albumin, fibronectin, and fibrinogen . Safety studies confirmed transient immune responses and no cumulative toxicity . LIPID-168 represents a promising non-viral platform for curative gene therapies in blood disorders.

EB-Lipid is an innovatively engineered ionizable lipid designed to replace conventional PEG-lipid in mRNA vaccine formulations. Its structure comprises three key components: an Evans Blue-derived headgroup with high affinity for albumin, a tetraethylene glycol linker that enhances colloidal stability, and dual oleate tails for anchoring into lipid bilayers. This molecular design enables EB-Lipid to actively recruit endogenous albumin, forming an albumin-rich protein corona on the surface of lipid nanoparticles (LNPs). Following intramuscular administration, these albumin-bound EB-LNPs are preferentially transported through lymphatic vessels rather than entering the bloodstream, thereby avoiding hepatic accumulation and associated hepatotoxicity risks.Experimental data demonstrate that EB-LNPs achieve significantly higher accumulation in lymph nodes, where they are efficiently internalized by dendritic cells via albumin receptor-mediated endocytosis (e.g., gp60). This process enhances antigen presentation and activates robust cellular and humoral immune responses. In both tumor models (B16-OVA and HPV-associated) and infectious disease models (H1N1 and SARS-CoV-2 Omicron), EB-LNP-based mRNA vaccines elicited potent cytotoxic T-cell activation and durable neutralizing antibody production at low doses. Unlike traditional PEG-LNPs, EB-LNPs show minimal liver distribution, reduced immunogenicity, and improved safety profiles after repeated administrations.By leveraging albumin’s natural trafficking pathway, EB-Lipid represents a transformative delivery platform that combines targeted lymph node delivery with enhanced biosafety, positioning it as a promising candidate for next-generation mRNA vaccines and therapeutics.

AA76-lipid is a dipeptide-modified ionizable lipid, engineered with an arginine-histidine motif, that constitutes the core of the pancreatic-targeted AH-LNP delivery platform. Its chemical architecture, characterized by an externally positioned and C-terminally modified arginine residue, was identified through systematic screening as the optimal structure for function. Upon intraperitoneal administration, AH-LNPs formulated with this lipid interact with proteins in the peritoneal fluid, undergoing dynamic assembly into significantly larger complexes. This substantial increase in size (from ~100 nm to over 360 nm) exploits a physical targeting principle termed the Capsule-filter-mediated pancreatic targeting (CAMP) mechanism. Large particles are selectively filtered out by the dense capsules of other abdominal organs, leading to preferential enrichment in the capsule-deficient pancreas. Concurrently, the arginine-histidine motif directs the formation of a distinct protein corona enriched with apolipoproteins (e.g., APOE, APOB-100), which mimics very-low-density lipoprotein (VLDL). This corona enables efficient cellular internalization primarily into pancreatic stromal cells via VLDL receptor (VLDLR)-mediated endocytosis, known as the VMP pathway. The synergistic integration of the physical CAMP targeting and the biological VMP uptake mechanisms empowers AA76-lipid-based AH-LNPs to achieve highly specific, potent, and sustained mRNA delivery and gene editing within the pancreas across multiple species, demonstrating exceptional therapeutic efficacy in models of both autoimmune pancreatitis and pancreatic cancer.

SAINT-2 is a cationic lipid with gene transfection activity and is a pyridyl lipid analog. Molecular membranes prepared by SAINT-2 can interact with plasmids to form lipid complexes. After the complex is taken up by cells, the plasmid dissociates from the lipid complex under the action of DOPE and the plasmid translocates across the endosome and/or nuclear membrane. Thus, SAINT-2 effectively transfers small oligonucleotides into cells。

DMT7 (pKa 6.5) is an ionizable cationic lipid engineered for co-delivery of mRNA and immunomodulators via LNPs. In 4T1 breast cancer metastasis models, DMT7 LNPs carrying IL-12 mRNA and STING agonist MSA-2 significantly reduce tumor burden and pulmonary metastases while modulating T cell populations. The formulation demonstrates broad immunotherapeutic effects in melanoma models, shifting tumor macrophages toward the M1 phenotype, reducing Tregs, and elevating pro-inflammatory cytokines (IL-12, IL-2, TNF-α, IFN-γ).

7-1 lipid represents a novel ionizable cationic compound designed for nucleic acid delivery applications.

DOIC is a cationic lipid that can be used for RNA vaccines.

DMDHP ((±)-Dimyristoyl-2,3-dimethylhydroxypropylamine) is a cationic lipid with a polar head group containing a dihydroxy group. DMDHP exhibits superior transfection efficiency and lower toxicity at high DNA doses in mouse intrapulmonary transfection model. DMDHP is commonly used for gene delivery.

APL-719 is a cationic lipid that can be used to synthesize lipid nanoparticles for drug delivery.

Lipid 29d is an ionizable lipid containing a thiophene moiety (Thio-lipid) for mRNA delivery. Lipid 29d enables LNPs to transfect the lung and spleen.

MIC1 is a set of multi-charged lipids with four tertiary amino nitrogen atoms (4N4T) which could be constructed and applied to form novel lipid nanoparticles. 4N4T-LNPs based on MIC1 exhibit much higher mRNA translation efficiency than the approved SM-102-LNPs. 4N4T-LNPs are successfully applied to DS mRNA vaccine and the vaccines worked well against SARS-CoV-2 and its variants, including Delta and Omicron.

Lipid 1 HG3 serves as a key component in LNPs specifically engineered for in vivo delivery of closed-end DNA (ceDNA), demonstrating efficient nucleic acid encapsulation and targeted release capabilities.

VC1052 is the component of Vaxfectin. Vaxfectin is a cationic lipid-based adjuvant that can be used for plasmid DNA- and protein-based vaccines.

DMHAPC-Chol is a cationic cholesterol. Liposomes containing DMHAPC-chol have been used for DNA plasmid delivery in vitro and in vivo in a B16-F10 mouse xenograft model. Liposomes containing DMHAPC-chol are cytotoxic to B16-F10 cells. DMHAPC-Chol, as part of a lipoplex with DOPE, has also been used to deliver DNA into mouse lung via intratracheal injection, resulting in a heterogeneous distribution in the bronchi and bronchioles, and to deliver VEGF siRNA into A431 and MDA-MB-231 cells, which secrete VEGF.

Vaxfectin is a cationic lipid-based adjuvant that can be used for plasmid DNA- and protein-based vaccines.

G0-C14 analog is a derivative of the ionizable cationic lipid G0-C14.

Lipid 20b​​ is a thiophene-based ionizable lipid synthesized via the Gewald reaction. It features dual unsaturated linoleic tails (C18:2) attached to the same side of the thiophene core and a tertiary amine headgroup. Formulated into LNPs (~100 nm, PDI ~0.2) with DSPC/cholesterol/DMG-PEG, it exhibits high mRNA encapsulation (>90%). Unlike traditional lipids, 20b lacks a pH-dependent ionization profile, likely due to electron delocalization in the thiophene ring. Intravenously, 20b LNPs transfect the liver and spleen in mice. Notably, subretinal delivery in mice and non-human primates (NHPs) achieved robust mRNA expression in photoreceptors (35% rods, 45% cones at high dose) and retinal pigment epithelium (RPE) with minimal acute toxicity. Immunosuppression enhanced rod transfection efficiency. High-dose administration in NHPs caused subretinal debris, but low doses (2.5 µg mRNA) maintained retinal health. This lipid demonstrates potential for liver and retinal gene therapy.

C10-200-based LNPs show enhanced liver tropism for mRNA delivery, outperforming branched-chain lipidoids (e.g., C12-200) in hepatic reporter gene expression. The system's therapeutic potential is confirmed through successful EPO production, with measurable increases in circulating protein levels following administration.

TS-202 is an ionizable lipid designed for mRNA vaccines, featuring a pH-responsive N-methylpiperidine head and a unique branched-tail structure with ester linkages to enable biodegradability. With a pKa of ~6.04–6.29, it facilitates efficient endosomal escape while maintaining stability in physiological conditions. Formulated into lipid nanoparticles (LNPs) of ~103 nm (PDI 0.08), L202 achieves >97% mRNA encapsulation efficiency. Its optimized structure drives robust immunogenicity: in mice, a single 0.1–10 μg dose induced dose-dependent SARS-CoV-2 spike-specific IgG titers, outperforming MC3-based LNPs and protein-alum vaccines. L202-LNPs elicited balanced Th1/Th2 responses (IgG2a/IgG1 ratio) and potent germinal center B cell activation, critical for durable immunity. Lyophilization with 16% sucrose preserved mRNA integrity and immunogenicity after 1-month storage at 5°C or 25°C, addressing cold-chain limitations. In nonhuman primates, two 100-μg doses generated neutralizing antibody titers exceeding convalescent human sera, with broad efficacy against Alpha, Beta, Gamma, and Delta variants. Rapid tissue clearance (72 hours post-injection) and minimal hepatic accumulation, attributed to ester hydrolysis, enhanced safety profiles. Additionally, L202-LNPs functioned as intrinsic adjuvants, amplifying protein vaccine responses. Combined with its lyophilization compatibility, potent cross-variant immunity, and favorable pharmacokinetics, L202 represents a promising platform for next-generation mRNA vaccines.

G9-1 is a nitric oxide (NO)-inhibitory ionizable lipid designed for anti-inflammatory mRNA delivery. Derived from the potent NO inhibitor G9, it retains the ability to suppress macrophage-driven inflammation while enabling efficient mRNA encapsulation and lung-targeted delivery. In a murine acute lung injury model, G9-1 lipid nanoparticles (LNPs) loaded with IL-10 mRNA demonstrated synergistic therapeutic effects by reducing inflammatory cell infiltration, suppressing pro-inflammatory cytokines, and improving systemic tissue injury markers. With its intrinsic immunomodulatory activity and preferential targeting of lung-resident cells, G9-1 represents a promising platform for safer and more effective mRNA therapeutics in inflammatory disorders.