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Angew Chem Int Ed Engl. 2012 Aug 20;51(34):8529-33. doi: 10.1002/anie.201203263. Epub 2012 Jul 10.

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

Author information

1
Alnylam Pharmaceuticals, Cambridge, MA, USA. mjayaraman@alnylam.com

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.

PMID:
22782619
PMCID:
PMC3470698
DOI:
10.1002/anie.201203263
[Indexed for MEDLINE]
Free PMC Article

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