In vivo silencing of Factor VII in liver hepatocytes.

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In vivo silencing of Factor VII in liver hepatocytes. In vivo silencing of Factor VII in liver hepatocytes. Nanoparticles were purified by dialysis, complexed with siRNA at a weight ratio of 10∶1 (nanoparticle:siRNA), and delivered intravenously to C57BL/6 mice. Mice received a single bolus administration of 5 mg/kg total siRNA via tail-vein injection and Factor VII levels were quantified 48 hr post injection. (A) Covalent attachment of cholesterol to C80 nanoparticles enabled silencing. Noncovalent encapsulation of cholesterol and delivery of control siGFP resulted in no knockdown. Data points represent group mean ± s.d. Data points marked with asterisks are significant relative to control treated groups (***, P < 0.0001; t-test, double-tailed, n = 14). Representative images of isolated organs for Cy5-siRNA-C80 (b) and Cy5-siRNA-C80-10 mol% cholesterol (C) nanoparticle complexes demonstrated nanoparticle accumulation in the liver, kidneys, and lungs after 120 min. The covalent attachment of cholesterol to C80 resulted in enhanced liver accumulation and reduced lung accumulation. Daniel J. Siegwart et al. PNAS 2011;108:32:12996-13001 ©2011 by National Academy of Sciences