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  • Title: Liver target delivery of small interfering RNA to the HCV gene by lactosylated cationic liposome.
    Author: Watanabe T, Umehara T, Yasui F, Nakagawa S, Yano J, Ohgi T, Sonoke S, Satoh K, Inoue K, Yoshiba M, Kohara M.
    Journal: J Hepatol; 2007 Dec; 47(6):744-50. PubMed ID: 17822798.
    Abstract:
    BACKGROUND/AIMS: RNA interference has considerable therapeutic potential, particularly for anti-viral therapy. We previously reported that hepatitis C virus (HCV)-directed small interfering RNA (siRNA; siE) efficiently inhibits HCV replication, using HCV replicon cells. To employ the siRNA as a therapeutic strategy, we attempted in vivo silencing of intrahepatic HCV gene expression by siE using a novel cationic liposome. METHODS: The liposomes consisted of conjugated lactose residues, based on the speculation that lactose residues would effectively deliver siRNA to the liver via a liver specific receptor. The lactosylated cationic liposome 5 (CL-LA5) that contained the most lactose residues introduced the most siRNA into a human hepatoma cell line, which then inhibited replication of HCV replicons. RESULTS: In mice, the siRNA/CL-LA5 complexes accumulated primarily in the liver and were widespread throughout the hepatic parenchymal cells. Moreover, siE/CL-LA5 specifically and dose-dependently suppressed intrahepatic HCV expression in transgenic mice without an interferon response. CONCLUSIONS: The present results indicate that the CL-LA5 we developed is a good vehicle to lead siRNA to the liver. Hence, CL-LA5 will be helpful for siRNA therapy targeting liver diseases, especially hepatitis C.
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