Lipid products — Page 37

H1L1A1B3 is an ionizable lipid which demonstrates a fourfold increase in circRNA transfection efficiency in lung cancer cells over ALC-0315. H1L1A1B31 is capable of proactively stimulating innate immune activation upon injection.

O12-D3-I3 is an imidazole-based lipid for siRNA delivery. O12-D3-I3-LNPs encapsulating FVII siRNA (FVII@O-LNP) elicites greater gene silencing than those with the DLin-MC3-DMA (MC3) due to its stronger endosomal escape.

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.

TG6A is a biodegradable and ionizable glycerolipid for cmRNA delivery. TG6A-LNP exhibits above 9-fold and 41-fold higher EGFP protein expression in MSCs than DLin-MC3-DMA-LNP and ALC-0315-LNP, respectively.

Si6-C14b is a siloxane-incorporated lipid for livertargeting mRNA delivery. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy.

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.

CL4F11_ζ-2 is an ionizable lipid for hepatic delivery of CRISPR/Cas ribonucleoprotein (RNP). CL4F11_ζ-2 LNP shows an extremely strong inhibitory effect of serum TTR protein levels compared with all the approved ionizable lipids including DLin-MC3-DMA (MC3), SM-102, and ALC-0315.

THP1 is a tetrahydropyrimidine ionizable lipid for mRNA delivery. THP1 demonstrates higher transfection efficiency comparable to DLin-MC3-DMA (MC3). THP1 LNPs also demonstrates the ability to edit genes in specific liver tissues in a tdTomato transgenic mouse model.

(+)CP-LC-0729 is an cationic lipid derived from CP-LC-0729 and achieves significantly higher expression and selectivity highlights the advantages of this lipid system for lung-targeted delivery.

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.

313O13 is an ionizable lipid with amine headgroups which drives LNP immunogenicity by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation. 313O13 prevents the often-observed loss of efcacy in the LNP-mediated delivery of siRNA and mRNA.

313oi10 is an ionizable lipid with amine headgroups which drives LNP immunogenicity by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation. 313oi10 prevents the often-observed loss of efcacy in the LNP-mediated delivery of siRNA and mRNA.

31hP is an asymmetric A3-lipid for mRNA delivery. 31hP LNP exhibits higher stability and durability compared with MC3 LNP and SM-102 LNP. 31hP LNP achieves more efficient hepatic mRNA delivery with a much higher gene editing efficiency than MC3 LNP and LP01 LNP.

A2C18_D5 is an optimized lipid nanoparticle (LNP) component engineered with structural modifications to enhance mRNA delivery efficiency and safety. Its design incorporates a hydrophobic head group (A2, featuring a pentyl chain) and an unsaturated C18 tail, which collectively lower its pKa to the ideal range of 6–7, enabling stable encapsulation of nucleic acids and improved endosomal escape. In vitro and in vivo studies demonstrate that A2C18_D5 achieves mRNA delivery efficiency comparable to the clinically approved LNP benchmark MC3, while exhibiting over 200-fold higher potency than its precursor lipid (A1C11). The lipid’s reduced protonation capacity minimizes cytotoxicity and hemolytic risk, aligning with safety profiles of established LNPs. Upon intravenous administration, A2C18_D5 predominantly targets the liver and spleen, with a biodistribution profile favoring hepatic delivery. Its balanced combination of high transfection efficiency, low toxicity, and favorable pharmacokinetics positions A2C18_D5 as a promising candidate for next-generation mRNA therapeutics, including vaccines and treatments for liver-specific diseases. Further optimization of its head-tail structure highlights its versatility for tailored delivery applications.

A3T2C7 (CP-LC-1495) is a biodegradable ionizable lipid featuring three β-propionate linkers and an azetidine polar head, formulated in four-component LNPs. It demonstrates exceptional lung-targeted mRNA delivery with 97.1% selectivity and high protein expression (1.21×10⁸ p/s) in mice. Its slightly positive zeta potential (~3.5 mV) correlates with lung tropism, likely mediated by protein corona enrichment of vitronectin and prothrombin. The β-propionate structure enables pH-sensitive biodegradability for enhanced endosomal escape while maintaining low cytotoxicity (>90% cell viability). This lipid enables organ-specific mRNA delivery without permanently charged additives, outperforming conventional SORT strategies in selectivity and expression efficiency.

F11T6 is a next-generation lipid nanoparticle (LNP) optimized for ultra-efficient neuron-targeted mRNA delivery, featuring a dual-tetrahydrofuran (THF) core and four pH-responsive acetal tails. Its unique bis-THF architecture enhances lipid bilayer stability and promotes brain-specific biodistribution, achieving ​​16.4% GFP+ neurons​​ in vivo—the highest reported among CNS-targeting LNPs. Cryo-EM reveals a compact spherical structure (Ø~150 nm) with 93.2% mRNA encapsulation efficiency, while THF-acetal synergy enables rapid endosomal escape (Pearson coefficient: 0.16 vs. 0.27 for F10T5). Preclinical studies show F11T6 leverages meningeal lymphatic transport for brain accumulation, yielding ​​13.0% neuron-specific tdTomato expression​​ in Ai14 mice, surpassing F10T5 (8.93%) and SM102 (0.1%). Mechanistically, the dual-THF core strengthens interactions with lipoprotein receptors on brain endothelial cells, whereas acetal tails undergo acid-triggered hydrolysis in endosomes, releasing mRNA into the cytoplasm. Despite slightly higher liver/spleen accumulation than F10T5, toxicology assessments confirm no hepatorenal toxicity (BUN/ALT/AST within normal ranges) or histopathological changes. Co-localization analyses demonstrate superior penetration into deep brain regions like the hippocampus, critical for treating neurodegenerative disorders. With a LogD of 12.3, F11T6 balances lipid solubility and biodegradability, outperforming clinical benchmarks in both efficiency (40× SM102) and neuron specificity. This platform holds transformative potential for delivering CRISPR-Cas9, siRNA, or neurotrophic factors, particularly in diseases demanding high-dose CNS transfection with minimal off-target effects.

THOR 76​​ is an ionizable lipid developed for lung-targeted mRNA delivery, synthesized via a high-throughput Ugi four-component reaction (U4CR). It combines spermine (N3, amine core), oleyl aldehyde (A2), oleic acid (C2), and a morpholine-functionalized isonitrile (D3). Remarkably, its ​​crude reaction mixture​​ outperforms purified forms in efficacy, suggesting synergistic impurities or intermediates enhance function. Formulated into lipid nanoparticles (LNPs) with cholesterol, DOPE, and PEG-lipid, THOR 76 LNPs exhibit ​​exceptional lung tropism​​ with secondary spleen affinity after intravenous administration. They efficiently transfect ​​pulmonary endothelial cells​​, enabling robust gene expression (e.g., Cre recombinase) and significant CRISPR-Cas9-mediated gene editing (1.22% at 0.1 mg/kg dose) in the lungs. With a particle size <150 nm, positive zeta potential, and >90% mRNA encapsulation, THOR 76 achieves targeted delivery while minimizing off-target effects in the liver. Its design overcomes limitations of cationic helper lipids, offering a potent, tolerable platform for treating pulmonary genetic disorders and cancers.

A33-D268 is an ionizable lipid derived from a 2-aminoimidazole (AM) core, featuring an asymmetric hydrophobic tail structure designed to optimize mRNA interactions. Selected as the top candidate from a 21-lipid library through molecular dynamics (MD) simulations, it demonstrated superior performance: low root mean square deviation (RMSD) and the smallest radius of gyration (Rg), indicating tight mRNA compaction, alongside moderate electrostatic energy and above-average hydrogen bonding for stable encapsulation. Formulated into LNPs, it achieves ​​efficient muscle-specific transfection​​ post-intramuscular injection, rivaling commercial ALC-0315 LNPs. Crucially, it exhibits ​​29-fold lower hepatic off-target expression​​, attributed to its inability to leverage serum protein coronas for liver tropism.

4A3-Cit is an ionizable lipid used for the generation of lipid nanoparticles (LNPs). To investigate the role of unsaturated lipid tails in iLNPs, the nucleophilic amines were added to ester-based linkers, followed by Michael’s addition to the thiols to construct a library of 91 amino ionizable lipids. Such ionizable lipids were composed of an ionizable tertiary amine core, an ester-based degradable linker, and an alkylthiol tail periphery. Through in vitro and in vivo screening, the iLNPs with 4A3 core and citronellolbased (Cit) periphery can significantly increase endosome escape and delivery efficiency of mRNA, leading to 18-fold increase in protein expression compared with iLNPs without Cit periphery. Furthermore, the delivery efficiency of mRNA may be associated with the location/configuration of the unsaturated bond(s) in lipids. Although lipids with Cit periphery showed excellent membrane fusion ability to facilitate endosome escape, the fusion mechanism needs to be further clarified.

G0-C14 is listed as a ionizable lipid for laboratory research use.