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ISSN 0582-9879 Acta Biochimica et Biophysica Sinica 2004, 36(7): 492–500 CN 31-1300/Q

Antitumor Effect of a Novel Adeno-associated Virus Vector Targeting to Telomerase Activity in Tumor Cells

Yi-Gang WANG1,2#, Jin-Hui WANG1#, Yan-Hong ZHANG1, Qing GU2*, and Xin-Yuan LIU1*

 

1Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China;
 2School of Life Science, Nanchang University, Nanchang 330047, China

 

Abstract        Telomerase activity is a wide tumor marker. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of the telomerase, is transcriptionally upregulated exclusively in about 90% of cancer cells. In this study, we constructed a novel adeno-associated virus (AAV) vector containing the human interferon-b (hIFN-b) gene under the control of hTERT promoter (AAV-hTERT-hIFN-b) and investigated its antitumor effect against various human cancer cells in vitro. AAV-hTERT-hIFN-b displayed cancer-specific hIFN-b expression and cytotoxicity. The cytotoxic ratio was positively correlated with the time length of infection. AAV-hTERT-hIFN-b-mediated apoptotic morphology was observed by transmission electron microscopy. Flow cytometry assay also revealed that the cytotoxicity of AAV-hTERT-hIFN-b was mainly an apoptotic process. These data indicate that AAV in combination with hTERT-mediated therapeutic gene expression may open new possibilities for long-lasting and targeting gene therapy of varieties of cancers.

 

Key words        adeno-associated virus (AAV); telomerase; hTERT promoter; human interferon-b; cancer

 

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Received: Match 17, 2004        Accepted: June 11, 2004

This work was supported by the grants from the Key Project of the Chinese Academy of Sciences (No. KSCX2-3-06), the National Natural  Science Foundation of China (No. 30120160823), and the National High Technology Research and Development Program of China (No. 2001AA217031)

#These authors contributed equally to this work

*Corresponding authors:

Xin-Yuan LIU: Tel, 86-21-54921127; Fax, 86-21-54921126; E-mail, [email protected]

Qing GU: Tel, 86-791-8305207; E-mail, [email protected]