1. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo.
- Author
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Jayaraman M, Ansell SM, Mui BL, Tam YK, Chen J, Du X, Butler D, Eltepu L, Matsuda S, Narayanannair JK, Rajeev KG, Hafez IM, Akinc A, Maier MA, Tracy MA, Cullis PR, Madden TD, Manoharan M, and Hope MJ
- Subjects
- Amines chemistry, Animals, Female, Genetic Therapy methods, Humans, Kinetics, Lipids chemistry, Liposomes administration & dosage, Liposomes chemistry, Liver metabolism, Mice, Mice, Inbred C57BL, Nanoparticles chemistry, RNA, Small Interfering chemistry, Gene Silencing, Lipids administration & dosage, Liver physiology, Nanoparticles administration & dosage, RNA, Small Interfering administration & dosage, RNA, Small Interfering genetics
- 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., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2012
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