Antitumor effect of a novel adeno-associated virus vector targeting to telomerase activity in tumor cells.

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-beta (hIFN-beta) gene under the control of hTERT promoter (AAV-hTERT-hIFN-beta) and investigated its antitumor effect against various human cancer cells in vitro. AAV-hTERT-hIFN-beta displayed cancer-specific hIFN-beta expression and cytotoxicity. The cytotoxic ratio was positively correlated with the time length of infection. AAV-hTERT-hIFN-beta-mediated apoptotic morphology was observed by transmission electron microscopy. Flow cytometry assay also revealed that the cytotoxicity of AAV-hTERT-hIFN-beta 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.

• Authors: Yi-Gang Wang, Jin-Hui Wang, Yan-Hong Zhang, Qing Gu, Xin-Yuan Liu
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 36 Issue 7 Pg. 492-500 (Jul 2004) ISSN: 1672-9145 [Print] China
• PMID: 15248024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Telomerase

Topics

• Apoptosis
• Cell Line
• DNA-Binding Proteins
• Dependovirus (genetics)
• Enzyme-Linked Immunosorbent Assay
• Genetic Vectors
• Humans
• Microscopy, Electron
• Reverse Transcriptase Polymerase Chain Reaction
• Telomerase (genetics, metabolism)