Small interfering RNA delivery to the liver by intravenous administration of galactosylated cationic liposomes in mice

Although small interfering RNA (siRNA) is a potentially useful therapeutic approach to silence the targeted gene of a particular disease, its use is limited by its stability in vivo. For the liver parenchymal cell (PC)-selective delivery of siRNA, siRNA was complexed with galactosylated cationic liposomes. Galactosylated liposomes/siRNA complex exhibited a higher stability than naked siRNA in plasma. After intravenous administration of a galactosylated liposomes/siRNA complex, the siRNA did not undergo nuclease digestion and urinary excretion and was delivered efficiently to the liver and was detected in PC rather than liver non-parenchymal cells (NPC). Endogenous gene (Ubc13 gene) expression in the liver was inhibited by 80% when Ubc13–siRNA complexed with galactosylated liposomes was administered to mice at a dose of 0.29 nmol/g. In contrast, the bare cationic liposomes did not induce any silencing effect on Ubc13 gene expression. These results indicated that galactosylated liposomes/siRNA complex could induce gene silencing of endogenous hepatic gene expression. The interferon responses by galactosylated liposomes/siRNA complex were controlled by optimization of the sequence of siRNA. Also no liver toxicity due to galactosylated liposomes/siRNA complex was observed under any of the conditions tested. In conclusion, we demonstrated the hepatocyte-selective gene silencing by galactosylated liposomes following intravenous administration.