Journal
JOURNAL OF HEPATOLOGY
Volume 47, Issue 6, Pages 744-750Publisher
ELSEVIER
DOI: 10.1016/j.jhep.2007.06.015
Keywords
siRNA; HCV; cationic liposome; lactosylation; target delivery; hepatocyte; liver; transgenic mouse; interferon
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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. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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