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A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent

Oncogene volume 23, pages 457–464 (2004)Cite this article

Abstract

Telomerase is a therapeutic target for cancer. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of the telomerase, is transcriptionaly upregulated exclusively in about 90% of cancer cells. Previous studies have demonstrated that hTERT promoter can control the expression of exogenous genes to the telomerase-positive cancer cells, thus hTERT promoter is an excellent candidate for generating cancer-specific oncolytic adenovirus. In this study, we devised a novel oncolytic adenovirus (Ad.TERT) by replacing the normal E1A regulatory elements with hTERT promoter. Ad.TERT displays cancer-specific E1A expression, virus replication and cytolysis in in vitro experiments. In animal experiments, intratumoral administration of Ad.TERT demonstrates potent antitumoral efficacy at least in two xenograft models (Bcap37 and BEL7404). Ad.TERT was targeted by the telomerase activity in cancer cells and has potent antitumoral efficacy in vivo, and since telomerase activity is a wide-ranged tumor marker, Ad.TERT could be a powerful therapeutic agent for a variety of cancers.

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Acknowledgements

We thank Bingliang Fang for providing us with the hTERT promoter. We also thank Lanyin Sun for help in the cell culture, Weijing Xu and Binghua Li for critical reading and discussion of this paper. This work was supported by the Key Project of the Chinese Academy of Sciences (No. KSCX2-3-06), the National Natural Science Foundation of China (No.30120160823), and the State 863 High Technology R&D Project of China (No. 2001AA217031).

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Authors and Affiliations

  1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, 200031, China

    Weiguo Zou, Chunxia Luo, Zilai Zhang, Jing Liu, Jingfa Gu, Zifei Pei & Xinyuan Liu

  2. Department of Medicine, Medical School, University of Navarra, Pamplona, 31080, Spain

    Cheng Qian

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  1. Weiguo Zou
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Correspondence to Xinyuan Liu.

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Zou, W., Luo, C., Zhang, Z. et al. A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent. Oncogene 23, 457–464 (2004). https://doi.org/10.1038/sj.onc.1207033

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