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Telomerase allows the immortalization of T antigen-positive DMD myoblasts: a new source of cells for gene transfer application

Gene Therapy volume 7, pages 619–623 (2000)Cite this article

Abstract

The limited proliferative capacity of DMD myoblasts severely limits their ability to be genetically modified and used for myoblast transplantation. Transformation by SV40 large T antigen (Tag) delays senescence of mouse and human myoblasts but fails to immortalize these cells. The cells ceased to proliferate and entered into crisis. Reconstitution of telomerase activity has been shown sufficient to enable different types of transformed cells to escape crisis. DMD myoblasts, previously transformed by Tag, were therefore infected with a telomerase retrovirus. The expression of telomerase was sufficient to allow DMD-Tag myoblasts to escape crisis. The telomerase-positive transformed myoblasts continued to divide for more than 55 doublings while Tag myoblasts stopped proliferating after 35 doublings. These cells are able to fuse and to differentiate normally. The average telomere length of these telomerase-positive DMD-Tag myoblasts seems to continue to elongate. Thus, transiently genetically modified myoblasts could constitute an important pool of DMD myoblasts for autologous transplantation in DMD patients.

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Acknowledgements

We thank F Tardif, M Goulet and B Roy for technical assistance, Drs P Leboulch (Masschusetts Institute of Technology, Cambridge) and W Wright (Department of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center) for their generous gifts. This work was supported by the Association Française contre les Myopathies (AFM) and the Muscular Dystrophy Association (MDA) and The National Institute On Aging (Ago 1992).

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  1. Laboratoire de Génétique Humaine, Université Laval and CHUQ Pavillon CHUL, 2705 Boulevard Laurier, Ste Foy (Qc), G1V4G2, Canada

    S Seigneurin-Venin, V Bernard & J P Tremblay

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  1. S Seigneurin-Venin
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  2. V Bernard
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  3. J P Tremblay
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Seigneurin-Venin, S., Bernard, V. & Tremblay, J. Telomerase allows the immortalization of T antigen-positive DMD myoblasts: a new source of cells for gene transfer application. Gene Ther 7, 619–623 (2000). https://doi.org/10.1038/sj.gt.3301132

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