GVS-18-B34 is a highly potent, silicon ether-based ionizable lipid that enables efficient mRNA delivery via lipid nanoparticles (LNPs). Its key advantage lies in a biodegradable silyl ether linkage, which undergoes rapid, non-enzymatic hydrolysis, leading to near-complete clearance from the liver within 24 hours in both mice and non-human primates (NHPs). This degradation mechanism is species-agnostic, overcoming the variability associated with esterase-dependent lipids. In vivo, GVS-18-B34 LNPs demonstrated superior liver-specific protein expression and a high liver-to-spleen signal ratio, indicating minimal off-target accumulation and reduced immune stimulation compared to benchmarks like MC3 and SM-102. The LNPs exhibited excellent stability when stored frozen at -80°C, maintaining integrity over multiple freeze-thaw cycles. With its optimal pKa (~6.3) and efficient endosomal escape profile, GVS-18-B34 represents a promising candidate for therapeutic applications requiring frequent dosing, combining high potency with a favorable safety profile derived from its rapid clearance.
