BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Inhibition of HBV replication and gene expression in vitro and in vivo with a single AAV vector delivering two shRNA molecules

  • Li, Zhi (Department of Microbiology, The University of Hong Kong) ;
  • He, Ming-Liang (Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Yao, Hong (Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Dong, Qing-Ming (Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Chen, Yang-Chao (Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Chan, Chu-Yan (Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Zheng, Bo-Jian (Department of Microbiology, The University of Hong Kong) ;
  • Yuen, Kwok-Yung (Department of Microbiology, The University of Hong Kong) ;
  • Peng, Ying (The Department of Neurology, The Second Affiliated Hospital, Sun Yat-sen University) ;
  • Sun, Qiang (Genetic Laboratory of Development and Diseases, Institute of Biotechnology) ;
  • Yang, Xiao (Genetic Laboratory of Development and Diseases, Institute of Biotechnology) ;
  • Lin, Marie C. (Department of Chemistry, The University of Hong Kong) ;
  • Sung, Joseph J.Y. (Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Kung, Hsiang-Fu (Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong)
  • 발행 : 2009.01.31
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초록

Hepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by $87{\pm}4$, $80.3{\pm}2.6$ and $86.2{\pm}7%$ respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.

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