A murine model of hepatitis B-associated hepatocellular carcinoma generated by adeno-associated virus-mediated gene delivery

Ya Hui Huang, Cheng Chieh Fang, Koichi Tsuneyama, Ho Yuan Chou, Wen Yu Pan, Yao Ming Shih, Ping Yi Wu, Yin Chen, Patrick S.C. Leung, M. Eric Gershwin, Mi Hua Tao

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19 引文 斯高帕斯(Scopus)

摘要

A relevant animal model is critical for investigating the pathogenic mechanisms underlying hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Mice are not naturally infected by HBV, presumably due to the lack of HBV receptors on mouse hepatocytes. To bypass this entry step of HBV infection, we report generation of a novel HBV model in immunocompetent mice by hepatic delivery of the HBV genome using trans-splicing adeno-associated viral vectors (AAV/HBV). We confirmed production of HBV virions and proteins in the liver and circulation in all AAV/HBV-transduced mice in all four immunocompetent mouse strains tested. These mice produced antigen and antibody profiles similar to that observed in chronic HBV patients. Importantly, 12-16 months later, all 12 AAV/HBV-transduced mice developed macroscopically visible liver-tumor nodules. Ten of the twelve tumors were characterized with typical HCC features. This AAV/HBV-transduced murine HCC model provides a useful instrument for studying the pathogenesis of HBV-associated HCC and the development of HCC therapeutic interventions.
原文英語
頁(從 - 到)1511-1519
頁數9
期刊International Journal of Oncology
39
發行號6
DOIs
出版狀態已發佈 - 十二月 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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