ARV-T1

ARV-T1 is a novel ionizable lipid featuring a cholesterol moiety incorporated in its tail, designed to enhance mRNA delivery efficiency. With a pKa of 6.73, it exhibits optimal pH-dependent ionization for endosomal escape and mRNA release. Structurally, ARV-T1 contains a tertiary amine head group and ester-linked lipid tails, enabling rapid in vivo metabolism and improved biocompatibility.Compared to SM-102 (used in Moderna's vaccine), LNPs formulated with ARV-T1 demonstrate superior physicochemical properties: smaller particle size (~80 nm vs. 90 nm), lower polydispersity index (0.09 vs. 0.10), and higher absolute zeta potential (-10 mV vs. -5 mV). These characteristics correlate with >90% mRNA encapsulation efficiency and enhanced stability, maintaining performance for 12 weeks at -20°C.In vitro, ARV-T1 LNPs showed 7-fold higher protein expression than SM-102 LNPs. In vivo, they prolonged luciferase expression (>72 hours vs. <48 hours for SM-102) and induced 10-fold higher neutralizing antibodies against SARS-CoV-2 spike protein at low doses. The cholesterol tail promotes endosomal membrane fusion, while ester linkages facilitate metabolic clearance, yielding an excellent safety profile in toxicity studies. This combination of efficacy and safety positions ARV-T1 as a promising platform for mRNA vaccines and therapeutics.