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Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector

Gene Therapy volume 8, pages 1043–1050 (2001)Cite this article

Abstract

We scrutinized the applicability and efficacy of Sendai virus (SeV) vectors expressing either LacZ or human insulin-like growth factor-I (hIGF-I) in gene transfer into skeletal muscle. Seven days after the intramuscular injection of LacZ/SeV X-gal labeled myofibers were demonstrated in rat anterior tibialis muscle with/without bupivacaine treatment and the transgene expression persisted up to 1 month after injection. Recombinant hIGF-I was detected as a major protein species in culture supernatants of a neonatal rat myoblast cell line L6 and thus induced the cells to undergo myogenetic differentiation. The introduction of hIGF-I/SeV into the muscle showed a significant increase in regenerating and split myofibers which were indicative of hypertrophy, and also an increase in the total number of myofibers, in comparison to that seen in the LacZ/SeV-treated control muscle. These results demonstrate that SeV achieves high-level transgene expression in skeletal muscle, and that hIGF-I gene transfer using SeV vector may therefore have great potential in the treatment of neuromuscular disorders.

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Acknowledgements

We acknowledge B. Moss for supplying vTF7-3, and D. Kolakofsky for supplying pGME-N, pGEM-P and pGEM-L.

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan

    A Shiotani, H Fukuda, K Saito & J Kanzaki

  2. DNAVEC Research Inc., Tsukuba, Japan

    M Fukumura, X Hou, M Inoue, T Kanamori, S Komaba, K Washizawa, S Fujikawa, T Yamamoto & M Hasegawa

  3. First Department of Anatomy, Osaka City University Medical School, Osaka, Japan

    M Maeda & C Kadono

  4. Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan

    K Watabe

  5. Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Y Sakai & Y Nagai

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  1. A Shiotani
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  2. M Fukumura
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  3. M Maeda
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  10. T Yamamoto
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  11. C Kadono
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  12. K Watabe
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  13. H Fukuda
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  14. K Saito
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  15. Y Sakai
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  16. Y Nagai
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  17. J Kanzaki
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  18. M Hasegawa
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Shiotani, A., Fukumura, M., Maeda, M. et al. Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector. Gene Ther 8, 1043–1050 (2001). https://doi.org/10.1038/sj.gt.3301486

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  • DOI: https://doi.org/10.1038/sj.gt.3301486

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