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Regulation of transgene expression in muscles by ultrasound-mediated hyperthermia

Gene Therapy volume 11, pages 894–900 (2004)Cite this article

Abstract

Heat-sensitive transgene expression systems have been proposed recently for use in gene therapy to enable both spatial and temporal control of the gene activity. The transgene was put under the control of HSP-related promoters and could be turned on by external heat treatment. While the ‘heat activation’ phenomenon of the HSP-related promoters in vitro had been well documented, the detailed time response and temporal regulation profile in vivo were not fully understood. We reported here the regulation of transgene luciferase expression in vivo in muscles using a custom-built ultrasound-mediated hyperthermia instrument. The effects of different heating parameters and treatment regimens were evaluated. Optimal activation of gene expression was found at 39°C. Significant tissue damage was observed at 41°C and above, which directly correlated with the greatly reduced gene expression. The gene constructs remained stable and silent in muscle cells, and could be turned on at a later time without losing much activity. Repeated activation was also possible, but required heat treatment at a higher temperature to overcome thermotolerance.

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Acknowledgements

We thank Professor Fucheng Sun for his technical supports in building the ultrasound-mediated hyperthermia system for the in vivo studies. This work was supported by the QiMingXing Young Investigator Award 00QA14014 to YHX.

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Authors and Affiliations

  1. School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China

    L Xu & Y Xu

  2. School of Life Science & Technology, Shanghai JiaoTong University, Shanghai, People's Republic of China

    Y Zhao, Q Zhang & Y Li

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Xu, L., Zhao, Y., Zhang, Q. et al. Regulation of transgene expression in muscles by ultrasound-mediated hyperthermia. Gene Ther 11, 894–900 (2004). https://doi.org/10.1038/sj.gt.3302254

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