Adenovirus-mediated gene transfer of interferon α improves dimethylnitrosamine-induced liver cirrhosis in rat model

K. Suzuki, K. Aoki, S. Ohnami, K. Yoshida, T. Kazui, N. Kato, K. Inoue, M. Kohara, T. Yoshida


36 被引用数 (Scopus)


Several lines of evidence suggest that interferon (IFN)-α is effective in suppression of liver cirrhosis (LC) as well as hepatitis C virus (HCV) infection, which is a major cause of LC in Japan. However, IFN-α often causes systemic toxicity such as flu-like symptoms, which precludes the IFN-α dose escalation required for clinical efficacy. Since IFN-α is rapidly degraded in the blood circulation, only a small amount of subcutaneously injected IFN-α protein can reach the target organ, the liver. It is expected that on-site IFN-α production in the liver overcomes the limitation of the conventional parenteral IFN-α administration. An adenovirus vector expressing the rat IFN-α gene (AxCA-rIFN) was injected intravenously into rats with dimethylnitrosamine-induced LC. While the subcutaneous IFN-α protein injection led to a transient elevation of the cytokine both in the liver and serum, the vector-mediated IFN-α gene transduction induced a significant amount of IFN-α detected in the liver but not in the serum. The injection of AxCA-rIFN prevented the progression of the rat LC, and improved the survival rate of the treated rats. Although no significant toxicity was noted in the animals, we showed that IFN-α gene expression in the liver can be efficiently downregulated by the Cre/loxP-mediated shut-off system, in case the IFN-α overdose becomes a problem. The study suggested for the first time the advantage and feasibility of IFN-α gene therapy for LC.

ジャーナルGene Therapy
出版ステータスPublished - 5月 2003

ASJC Scopus subject areas

  • 分子医療
  • 分子生物学
  • 遺伝学


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