VC-LC-0743 is an ionizable lipid engineered for lipid nanoparticle (LNP) delivery systems, featuring a pH-responsive morpholine/piperazine-derived headgroup that enables protonation in acidic endosomes to facilitate mRNA release. Its structure integrates a central thioether (-S-) linkage for enhanced stability, ester/amide bonds to promote enzymatic biodegradability, and branched C10-C22 alkyl chains (e.g., 2-hexyldecyl) to optimize membrane fusion and RNA encapsulation efficiency. Preclinical studies demonstrate robust in vivo transfection, achieving sustained protein expression (e.g., luciferase or antigens) at low RNA doses with minimal cytotoxicity. The lipid’s apparent pKa (~6.5-6.8) balances neutral charge at physiological pH for reduced immunogenicity and positive charge in endosomes for efficient cytosolic delivery. VC-LC-0743-based LNPs exhibit superior thermal stability (≥3 months at 4°C) and outperform commercial analogs (e.g., ALC-0315) in both potency and expression duration. Its design aligns with Formula (I) in the patent, emphasizing controlled degradation via ester/thioether cleavage to mitigate systemic toxicity. These attributes position VC-LC-0743 as a versatile candidate for mRNA vaccines, gene therapies, and targeted oncology applications, with scalable synthesis supporting clinical translation. Further studies focus on organ-specific tropism and long-term safety profiles.
Cat.No
DC60847
Name
Moderna VC-LC-0743
Chemical Properties
CAS
Formula
C45H87O4N3S
MW
766.27
Storage
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
References
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