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Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA.

Authors
  • Sakamoto, Naoya1
  • Tanabe, Yoko
  • Yokota, Takanori
  • Satoh, Kenichi
  • Sekine-Osajima, Yuko
  • Nakagawa, Mina
  • Itsui, Yasuhiro
  • Tasaka, Megumi
  • Sakurai, Yuki
  • Cheng-Hsin, Chen
  • Yano, Masahiko
  • Ohkoshi, Shogo
  • Aoyagi, Yutaka
  • Maekawa, Shinya
  • Enomoto, Nobuyuki
  • Kohara, Michinori
  • Watanabe, Mamoru
  • 1 Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan. [email protected] , (Japan)
Type
Published Article
Journal
Journal of Gastroenterology and Hepatology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 01, 2008
Volume
23
Issue
9
Pages
1437–1447
Identifiers
PMID: 17683479
Source
Medline
Language
English
License
Unknown

Abstract

We have reported previously that synthetic small interfering RNA (siRNA) and DNA-based siRNA expression vectors efficiently and specifically suppress hepatitis C virus (HCV) replication in vitro. In this study, we investigated the effects of the siRNA targeting HCV-RNA in vivo. We constructed recombinant retrovirus and adenovirus expressing short hairpin RNA (shRNA), and transfected into replicon-expressing cells in vitro and transgenic mice in vivo. Retroviral transduction of Huh7 cells to express shRNA and subsequent transfection of an HCV replicon into the cells showed that the cells had acquired resistance to HCV replication. Infection of cells expressing the HCV replicon with an adenovirus expressing shRNA resulted in efficient vector delivery and expression of shRNA, leading to suppression of the replicon in the cells by approximately 10(-3). Intravenous delivery of the adenovirus expressing shRNA into transgenic mice that can be induced to express HCV structural proteins by the Cre/loxP switching system resulted in specific suppression of virus protein synthesis in the liver. Taken together, our results support the feasibility of utilizing gene targeting therapy based on siRNA and/or shRNA expression to counteract HCV replication, which might prove valuable in the treatment of hepatitis C.

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