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A calcium-sensitive promoter construct for gene therapy

Gene Therapy volume 20, pages 248–254 (2013)Cite this article

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Abstract

Targeting diseased cells is a challenging issue in both pharmacological and biological therapeutics. Gene therapy is emerging as a novel approach for treating rare diseases and for illnesses for which there is no other alternative. An important limitation of gene therapy has been the off-target effects and therefore efforts have been focused on increasing the specificity of gene transfer to the targeted organ. Here, we describe a promoter containing six nuclear factor of activated T cells (NFAT) consensus sequences, which is as efficient as the cytomegalovirus (CMV) promoter to drive expression in vascular smooth muscle cells both in vitro and in vivo. In contrast to the CMV promoter it is activated in a Ca2+-dependent manner after endoplasmic reticulum depletion and allows the transgene expression only in proliferative/diseased cells. Overexpression of sarco/endoplasmic reticulum (SR/ER) Ca2+ ATPase 2a under the control of this NFAT promoter inhibits restenosis after angioplasty in rats. In conclusion, this promoter may be useful for gene therapy in vascular proliferative diseases and other diseases involving upregulation of the NFAT pathway.

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Acknowledgements

This work was supported by Association Française contre les Myopathies (AFM). Dr Marchand and Dr Lompré were supported by the Leducq Foundation. Dr Lipskaia is supported by AHA SDG 0930116N. Dr Lompré benefits of a contract with Assistance publique-hôpitaux de Paris. Elise Merlet was supported by the French Ministry of research and education.

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Author notes

  1. E Merlet and L Lipskaia: These authors equally contributed to this work.

Authors and Affiliations

  1. Transatlantic Cardiovascular Research Center, INSERM UMRS 956, UPMC-Paris 6, Paris, France

    E Merlet, L Lipskaia, A Marchand, F Atassi, S N Hatem & A-M Lompré

  2. PECMV IFR14, UPMC-Paris 6, Paris, France

    N Mougenot

  3. Transatlantic Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, USA

    L Lipskaia, L Hadri, L Liang & R J Hajjar

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  1. E Merlet
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Correspondence to A-M Lompré.

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Merlet, E., Lipskaia, L., Marchand, A. et al. A calcium-sensitive promoter construct for gene therapy. Gene Ther 20, 248–254 (2013). https://doi.org/10.1038/gt.2012.30

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