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Acta Biochimica et Biophysica Sinica Advance Access originally published online on May 27, 2009
Acta Biochimica et Biophysica Sinica 2009 41(7):554-560; doi:10.1093/abbs/gmp044
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Treatment of hepatitis C virus core-positive hepatocytes with the transfer of recombinant caspase-3 using the 2',5'-oligoadenylate synthetase gene promoter

Ying Wang1, Shanshan Mao2, Bo Li1, Pingping Tan1, Deyun Feng1,* and Jifang Wen1,*

1 Department of Pathology, Basic Medical College, Central South University, Changsha 410078, China
2 Department of Pathology, Shanghai Medical School, Fudan University, Shanghai 200032, China

* Correspondence address. Tel: +86-731-2650410; Fax: +86-731-2650408; E-mail: dyfeng743{at}yahoo.com.cn (D.F.); Tel: +86-731-2650400; Fax: +86-731-2650408; E-mail: jifangwen{at}hotmail.com (J.W.)


  Abstract

Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality throughout the world. There is no vaccine available and current therapy is only partially effective. Since HCV infects only a minority of hepatocytes, we hypothesized that induction of apoptosis might be a promising approach for the treatment of hepatitis C. In the present study, recombinant caspase-3 gene (re-caspase-3) was used because it has the ability to induce apoptosis that is independent of the initiator caspases. An HCV-specific promoter is required to regulate the cytotoxic caspase-3 expression in HCV-infected cells. It has been reported that HCV core protein can specifically activate the 2',5'-oligoadenylate synthetase (OAS) gene promoter in human hepatocytes. Therefore, we constructed an expression vector consisting of the re-caspase-3 under the OAS gene promoter (pGL3-OAS-re-caspase-3) and then investigated its effect on HCV core-positive liver cells. It was found that the pGL3-OAS-re-caspase-3 construct induced apoptosis in HCV core-positive liver cells, but not in normal liver cells. These results strongly suggested that the transfer of the re-caspase-3 gene under the OAS promoter was a novel targeting approach for the treatment of HCV infection.

Keywords    recombinant caspase-3; 2',5'-oligoadenylate synthetase; apoptosis; gene therapy

Received: February 15, 2009; Accepted: April 8, 2009
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