Adenoviral-vector mediated transfer of HBV-targeted ribonuclease can inhibit HBV replication in vivo

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• 作者：Ya Zhao ; Yinghui Li ; Jun Liu ; Zhongxiang Liu ; Yuxiao Huang ; Junchuan Lei ; Shumei Li ; Caifang Xue
• 关键词：HBV ; Gene therapy ; Adenovirus ; Targeted ribonuclease
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2008
• 出版时间：4 July 2008
• 年：2008
• 卷：371
• 期：3
• 页码：541-545
• 全文大小：794 K

文摘

Hepatitis B virus (HBV)-targeted ribonuclease (HBV-TR) is a fused protein of HBV core protein and a ribonuclease, human eosinophil-derived neurotoxin (hEDN). Our previous results showed that HBV-TR could effectively inhibit HBV replication in vitro. To test whether HBV-TR can inhibit HBV replication in vivo, we constructed a recombinant adenoviral vector expressing HBV-TR (Ad-TR) and used it to treat HBV-transgenic mice. Immunohistochemical staining showed that TR was expressed at varied levels in different tissues of Ad-TR-treated mice. Serum HBsAg concentration was decreased by 64.8 % for the Ad-TR-treated mice compared with empty adenoviral vector-treated control mice. The amount of HBV-DNA in the livers of the Ad-TR-treated mice was 0.74 × 10⁷ copies/μg of genomic DNA while the amount of HBV-DNA in the livers of the empty adenoviral vector-treated control mice was 2.86 × 10⁷ copies/μg of genomic DNA. Serum HBV-DNA of Ad-TR-treated mice was also decreased by 71.4 % compared with empty adenoviral vector-treated control mice. In addition, for some Ad-TR-treated mice, the expression of HBsAg in the liver cells turned negative. No discernible adverse effects were observed for Ad-TR-treated mice. Taken together, our results indicated that adenovirus mediated transfer of HBV-TR can inhibit HBV replication in vivo.