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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]