Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo
Muthusamy Jayaraman1, Steven M Ansell, Barbara L Mui
1Alnylam Pharmaceuticals, Cambridge, MA, USA. mjayaraman@alnylam.com
Angewandte Chemie (International Ed. in English)
|July 12, 2012
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.
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