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J Hepatol. 2007 Dec;47(6):744-50. Epub 2007 Jul 26.

Liver target delivery of small interfering RNA to the HCV gene by lactosylated cationic liposome.

Author information

  • 1Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.

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.

PMID:
17822798
[PubMed - indexed for MEDLINE]
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