Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo.
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ABSTRACT:
SUBMITTER: Jayaraman M
PROVIDER: S-EPMC3470698 | biostudies-literature | 2012 Aug
REPOSITORIES: biostudies-literature
Publications
Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo.
Jayaraman Muthusamy M Ansell Steven M SM Mui Barbara L BL Tam Ying K YK Chen Jianxin J Du Xinyao X Butler David D Eltepu Laxman L Matsuda Shigeo S Narayanannair Jayaprakash K JK Rajeev Kallanthottathil G KG Hafez Ismail M IM Akinc Akin A Maier Martin A MA Tracy Mark A MA Cullis Pieter R PR Madden Thomas D TD Manoharan Muthiah M Hope Michael J MJ
Angewandte Chemie (International ed. in English) 20120710 34
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. ...[more]
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