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Highly efficient EIAV-mediated in utero gene transfer and expression in the major muscle groups affected by Duchenne muscular dystrophy

Gene Therapy volume 11, pages 1117–1125 (2004)Cite this article

Abstract

Gene therapy for Duchenne muscular dystrophy has so far not been successful because of the difficulty in achieving efficient and permanent gene transfer to the large number of affected muscles and the development of immune reactions against vector and transgenic protein. In addition, the prenatal onset of disease complicates postnatal gene therapy. We have therefore proposed a fetal approach to overcome these barriers. We have applied β-galactosidase expressing equine infectious anaemia virus (EIAV) lentiviruses pseudotyped with VSV-G by single or combined injection via different routes to the MF1 mouse fetus on day 15 of gestation and describe substantial gene delivery to the musculature. Highly efficient gene transfer to skeletal muscles, including the diaphragm and intercostal muscles, as well as to cardiac myocytes was observed and gene expression persisted for at least 15 months after administration of this integrating vector. These findings support the concept of in utero gene delivery for therapeutic and long-term prevention/correction of muscular dystrophies and pave the way for a future application in the clinic.

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Acknowledgements

LG is funded by a grant from the Muscular Dystrophy Association, USA. This work has been supported by an MRC Programme Grant. SW is salary funded by the Katherine Dormandy Trust.

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Authors and Affiliations

  1. Gene Therapy Research Group, Sir Alexander Fleming Building, Imperial College, South Kensington, London, UK

    L G Gregory, S N Waddington, M V Holder, S M K Buckley, B W Bigger, L Lawrence, F Al-Allaf, C Coutelle & M Themis

  2. Department of Cell and Molecular Biology, Leukocyte Biology, Sir Alexander Fleming Building, Imperial College, South Kensington, London, UK

    L G Gregory, S N Waddington, M V Holder, S M K Buckley, B W Bigger, L Lawrence, F Al-Allaf & M Themis

  3. Oxford BioMedica (UK), Oxford, UK

    K A Mitrophanous, F M Ellard, L E Walmsley & S Kingsman

  4. Renal Medicine Section, Faculty of Medicine, Imperial College London, London, UK

    K L Mosley

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  1. L G Gregory
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  2. S N Waddington
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  3. M V Holder
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  10. L Lawrence
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  11. F Al-Allaf
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  14. M Themis
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Gregory, L., Waddington, S., Holder, M. et al. Highly efficient EIAV-mediated in utero gene transfer and expression in the major muscle groups affected by Duchenne muscular dystrophy. Gene Ther 11, 1117–1125 (2004). https://doi.org/10.1038/sj.gt.3302268

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  • DOI: https://doi.org/10.1038/sj.gt.3302268

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