Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo

Abstract

Special (lipid) delivery: The role of the ionizable lipid pKa in the in?vivo delivery of siRNA by lipid nanoparticles has been studied with a large number of head group modifications to the lipids. A tight correlation between the lipid pKa?value and silencing of the mouse FVII gene (FVII ED50) was found, with an optimal pKa range of 6.2-6.5 (see graph). The most potent cationic lipid from this study has ED50 levels around 0.005?mg?kg?1 in mice and less than 0.03?mg?kg?1 in non-human primates.