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Hypoxia-Specific Downregulation of Endogenous Human VEGF-A Gene by Hypoxia-Driven Expression of Artificial Transcription Factor

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Abstract

Repression of vascular endothelial growth factor A (VEGF-A) is an attractive approach to cancer therapy. Although zinc-finger-based artificial transcription factors (ATFs) were constructed for human VEGF-A and constitutive expressions of ATFs were previously shown to downregulate the endogenous VEGF-A gene expression, repression of VEGF-A specifically in hypoxic tumors is desirable for therapeutic application of ATF technology. Here, we describe hypoxia-driven expression of the ATF for hypoxia-specific repression of human VEGF-A gene. We constructed a hypoxia-driven promoter for the ATF expression and placed it upstream of the ATF-encoding region. The resulting hypoxia-driven expression plasmids induced the expression of ATFs specifically in hypoxia, and the hypoxia-specific expression of ATFs effectively downregulated the VEGF-A expression in hypoxia, but not in normoxia. Thus, the engineered expression system of ATFs may enable repression of VEGF-A expression specifically in hypoxic tumors without affecting normal, healthy tissues.

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Acknowledgements

We thank Haruyuki Atomi for the use of their DNA sequencer. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan to T.S.

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Authors and Affiliations

  1. Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo-ku, Kyoto, 615-8510, Japan

    Tomoaki Mori, Jun Sasaki, Yasuhiro Aoyama & Takashi Sera

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  1. Tomoaki Mori
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  2. Jun Sasaki
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  3. Yasuhiro Aoyama
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  4. Takashi Sera
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Correspondence to Takashi Sera.

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Mori, T., Sasaki, J., Aoyama, Y. et al. Hypoxia-Specific Downregulation of Endogenous Human VEGF-A Gene by Hypoxia-Driven Expression of Artificial Transcription Factor. Mol Biotechnol 46, 134–139 (2010). https://doi.org/10.1007/s12033-010-9288-z

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  • DOI: https://doi.org/10.1007/s12033-010-9288-z

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