Lipid products — Page 41

HTO12 is an ionizable cationic lipid (pKa ~6.43) specifically designed for mRNA encapsulation in lipid nanoparticles. When formulated with complementary lipids, it enables efficient nucleic acid delivery in both cellular systems and living organisms.

FTT5 LLNs is a modified TT3-derived lipidoid optimized for nucleic acid delivery via lipid-like nanoparticles (LLNs). These formulations demonstrate hepatic tropism in mice and enhance reporter gene expression in Hep3B cells. Therapeutically, FTT5 LLNs successfully deliver Factor VIII mRNA to restore clotting activity in hemophilic mice and enable in vivo genome editing applications.

CAP 2 is a unique ionizable lipid featuring a bicholesterol structure connected by a phosphate linker with an amino terminus. This design enables efficient in vivo delivery of both mRNA and saRNA via LNPs. In a Dmc1-deficient mouse model of male infertility, saRNA-encoded Dmc1 delivered by CAP 2 LNPs demonstrated prolonged protein expression in testicular tissue compared to mRNA formulations. The treatment restored spermatogenesis, improving germ cell maturation, seminiferous tubule morphology, and ultimately yielding functional sperm capable of fertilization.

Lipid C-1 is an ionizable cationic amino lipid structurally derived from SM-102, optimized for enhanced mRNA delivery. When formulated into LNPs, it demonstrates superior transfection efficiency in Calu-3 cells, driving significantly higher luciferase reporter expression compared to its parent compound.

Lipid VII is a novel ionizable cationic lipid developed by Sanofi.Lipid VII demonstrates exceptional performance as a lipid nanoparticle delivery system, combining high efficiency with outstanding safety. Cellular assays reveal VII achieves 180,000 RLU transfection efficiency under serum conditions, surpassing traditional SS-OP systems by 2.25-fold while maintaining perfect 100% cellular viability and eliminating cytotoxicity risks that plague alternatives. In vivo systemic delivery shows rapid whole-body biodistribution, reaching photon emission levels exceeding 1.00E+10 photons/sec within 48 hours. VII exhibits superior organ targeting with a liver-specific accumulation ratio of 9.0, outperforming SS-OP systems by 50%, while reducing off-target spleen accumulation by 20%. Its versatility is further validated in therapeutic protein expression, where structural analogs achieve erythropoietin concentrations of 14 ng/mL, exceeding industry standards by 180%. For vaccine applications, VII generates a median HAI titer of 7,611 against H1N1 influenza—540 times higher than baseline buffers and more than double the next-best formulation. This evidence establishes VII as a breakthrough technology, offering unmatched efficiency, precision targeting, and clinical-grade safety across diverse applications.

A1-28 is a redox-responsive ionizable lipid featuring a disulfide linkage, designed for CRISPR component delivery. Its LNP formulations effectively package both Cas9 mRNA and sgRNA, enabling efficient genome editing in cultured cells.

ALC-0315 N-oxide represents a potential oxidative degradation product that may be present in formulated batches of the cationic lipid ALC-0315.

Westgene lipid 8 is a cationic lipid featuring a tertiary amine core with three alkyl chains (C1-C15) and two unsaturated C18 linoleate-like tails. Its ionizable amine enables pH-dependent charge for mRNA encapsulation in LNPs. Key structural elements include branched alkyl groups (X1/X2: C4, X3: C2) and ester-linked unsaturated R1/R2 chains, enhancing membrane fusion and endosomal escape. N Used in lipid nanoparticles (LNPs) with DOPE, cholesterol, and PEG-DMG, it demonstrates low cytotoxicity, high mRNA delivery efficiency, and spleen-targeted immune activation, making it suitable for vaccine/therapeutic delivery.

SL02 is a next-generation ionizable lipid featuring a unique branched hydrophobic domain and a pH-sensitive dimethylaminoethyl headgroup（pKa 6.25）developed by Seqirus. Its asymmetric lipid tails, combining unsaturated and saturated chains, enhance LNP fusogenicity and endosomal membrane disruption. With a slightly lower pKa than SL01, SL02 achieves efficient mRNA binding at acidic pH while maintaining neutral charge in circulation, reducing nonspecific interactions. In vitro, SL02-LNPs show superior transfection potency in BHK-V cells, attributed to improved cellular uptake and endosomal escape kinetics. In vivo, it elicits high neutralizing antibody titers (comparable to MF59-adjuvanted vaccines) and robust CD8+ T-cell activation. The lipid’s ester-based design ensures biodegradability, while PEGylation compatibility enhances colloidal stability. SL02’s tailored balance of hydrophobicity and ionization enables precise control over nanoparticle size (70–120 nm) and low polydispersity, positioning it as a leading candidate for saRNA-based vaccines and gene therapies.

SL01 is an ionizable cationic lipid compound pKa 6.31）developed by Seqirus, characterized by a biodegradable ester backbone and tertiary amine headgroup, enabling pH-dependent charge modulation. Its structure incorporates twin hydrophobic tails with unsaturated carbon chains, enhancing membrane fluidity and promoting endosomal escape. The lipid’s pKa (~6.5–7.0) optimizes nucleic acid complexation at physiological pH while minimizing cytotoxicity. SL01 demonstrates robust mRNA encapsulation efficiency (~90%) in lipid nanoparticles (LNPs) and facilitates intracellular delivery via endocytosis. Preclinical studies highlight its efficacy in inducing potent humoral and cellular immune responses, particularly in influenza mRNA vaccines. Its ester linkages ensure gradual metabolic clearance, reducing long-term toxicity. SL01-based LNPs exhibit stability in serum and compatibility with scalable manufacturing processes, making it a versatile candidate for therapeutic mRNA delivery.

​​nor-MC3​​ is a novel ionizable lipid develoed by Nanovation, derived from the MC3 structural framework, characterized by two ​​C17 alkyl chains​​ (each containing two Z-geometry double bonds) conjugated to a ​​4-(dimethylamino)butanoate​​ headgroup. Synthesized via a streamlined route involving Claisen condensation of methyl linoleate, hydrolysis/decarboxylation to generate a C17 ketone, reduction to the corresponding alcohol, and final esterification with 4-(dimethylamino)butanoic acid, nor-MC3 retains the ionizable amine functionality critical for pH-dependent nucleic acid binding and endosomal escape. Compared to the benchmark lipid MC3 (C18 chains), nor-MC3 demonstrates ​​superior mRNA delivery efficiency​​ in vitro (2-fold higher luciferase expression at 10 μg/mL mRNA) and enhanced in vivo biodistribution (higher liver and spleen targeting in mice). Notably, its shortened C17 chains challenge conventional assumptions about optimal hydrophobic chain length, offering improved synthetic scalability while maintaining or exceeding MC3's encapsulation efficiency (~95%), nanoparticle size (~80 nm), and low polydispersity (PDI ~0.08). For siRNA delivery, nor-MC3 achieves comparable EC₅₀ values (0.1644 μg/mL vs. MC3’s 0.1308 μg/mL), highlighting its versatility as a next-generation lipid nanoparticle (LNP) component for nucleic acid therapeutics.

ATX-129 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

ATX-111 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

ATX-132 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

ATX-100 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

ATX-106 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.

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.

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.

HCQ-4​​ is a rationally engineered ionizable lipid derived from hydroxychloroquine (HCQ), featuring a ​​ditetradecylamine-derived twin-C14 saturated hydrocarbon tail​​ linked to the HCQ headgroup via a ​​succinic acid spacer​​. Synthesized through a three-step route involving HCQ deprotonation, ditetradecylamine carboxylation, and EDC/DMAP-mediated amidation, this lipid forms the core of optimized lipid nanoparticles (LNPs) at a molar ratio of ​​60:10:40:0.5 (HCQ-4:DOPE:cholesterol:DMG PEG 2000 )​​. The structure enables dual functionality: (1) ​​Spleen-selective mRNA delivery​​ (2.3-fold higher splenic vs. hepatic transfection) via 80-100 nm particle size, near-neutral charge (-3 mV), and low PEG density, facilitating immune cell uptake; (2) ​​Tumor microenvironment modulation​​ through HCQ-mediated repolarization of M2 macrophages to antitumor M1 phenotype (iNOS + cells ↑2.5-fold, CD206 + cells ↓60%). This bifunctional design synergistically enhances mRNA cancer vaccine efficacy, demonstrating superior prophylactic/therapeutic antitumor activity and antimetastatic effects compared to clinical benchmarks like MC-3 LNP.

ORNA lipid 144​​ is a novel ionizable lipid engineered for splenic RNA delivery developed by ORNA Therapeutics, featuring a biodegradable structure with a protonatable tertiary amine headgroup and ester-linked branched C14 alkyl chains. This design enables exceptional spleen-targeting capability, demonstrated by 3-fold higher luciferase expression in the spleen compared to benchmark lipids and near-complete B-cell depletion when delivering anti-CD19 CAR circRNA. It forms highly stable lipid nanoparticles maintaining homogeneous size (60–80 nm) and low polydispersity across diverse manufacturing conditions and buffer systems. Rapid clearance from the liver and spleen minimizes off-target accumulation, while high circRNA encapsulation efficiency (>90%) and pH-dependent endosomal escape make it ideal for immunotherapies and vaccines requiring precise splenic bioavailability and sustained efficacy.