Small Interfering Rna Delivery to the Liver by Intravenous Administration of Galactosylated Cationic Liposomes in Mice.
From: GeneCare Research Institute Co. Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-0063, Japan.
Biomaterials
- Publish Date: Mar 2007
- ISSN: 0142-9612
- Volume: 28
- Issue: 7
- Pages: 1434-42
- Medium: Print
- Language: English
- Citation (JAMA): Sato Ayumi, Takagi Motoki, Shimamoto Akira, et al. Small Interfering Rna Delivery to the Liver by Intravenous Administration of Galactosylated Cationic Liposomes in Mice.. Biomaterials Mar 2007;28:1434-42
Abstract
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.
Mesh Headings (Keywords): Animals, Biocompatible Materials, Cations, Chemistry, Physical, Drug Delivery Systems, Drug Stability, Galactose, Gene Silencing, Injections, Intravenous, Liposomes, Liver, Male, Materials Testing, Mice, Mice, Inbred ICR, RNA, Small Interfering
Check for Full Text / PubMed Unique Identifier (PMID): 17141864
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