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

ABSTRACT: Special (lipid) delivery: The role of the ionizable lipid pK(a) 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 pK(a) value and silencing of the mouse FVII gene (FVII ED(50) ) was found, with an optimal pK(a) range of 6.2-6.5. The most potent cationic lipid from this study has ED(50) levels around 0.005 mg kg(-1) in mice and less than 0.03 mg kg(-1) in non-human primates.

SUBMITTER: Jayaraman M 

PROVIDER: S-EPMC3470698 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature