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Enhanced expression of recombinant dystrophin following intramuscular injection of Epstein–Barr virus (EBV)-based mini-chromosome vectors in mdx mice

Gene Therapy volume 6, pages 1331–1335 (1999)Cite this article

Abstract

Gene transfer by direct intramuscular injection of naked plasmid DNA has been shown to be a safe, simple but relatively inefficient method for gene delivery in vivo. Eukaryotic plasmid expression vectors incorporating the Epstein–Barr virus (EBV) origin of replication (oriP) and EBNA1 gene have been shown to act as autonomous episomally replicating gene transfer vectors which additionally provide nuclear matrix retention functions. Prolonged expression of a LacZ reporter gene and recombinant human dystrophin was shown using EBV-based plasmid vectors transfected into C2C12 mouse myoblast and myotube cultures. Intramuscular injection of EBV-based dystrophin expression plasmids into nude/mdx mice resulted in significant enhancement in the number of muscle fibres expressing recombinant dystrophin compared with a conventional vector. This effect was observed for over 10 weeks after a single administration. These results indicate the potential advantage of EBV-based expression vectors for focal plasmid-mediated gene augmentation therapy in Duchenne muscular dystrophy (DMD) and a range of other gene therapeutic applications.

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Acknowledgements

This work was supported by the UK Medical Research Council, the Leopold Muller Trust and the Muscular Dystrophy Group of Great Britain and Northern Ireland.

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Authors and Affiliations

  1. Division of Biochemistry, School of Biological Sciences, Royal Holloway College, University of London, Egham, UK

    H Tsukamoto, S C Brown, P Serpente, J Drew & G Dickson

  2. Department of Pediatrics, Osaka University Medical School, Suita, Osaka, Japan

    H Tsukamoto, K Inui & S Okada

  3. Department of Neuromuscular Disease, Gene Targeting Unit, Imperial College School of Medicine, London

    D J Wells

  4. Division of Biomedical Sciences, Sheffield Hallam University, Sheffield, UK

    P N Strong

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  1. H Tsukamoto
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  2. D J Wells
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  6. J Drew
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  8. S Okada
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  9. G Dickson
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Tsukamoto, H., Wells, D., Brown, S. et al. Enhanced expression of recombinant dystrophin following intramuscular injection of Epstein–Barr virus (EBV)-based mini-chromosome vectors in mdx mice. Gene Ther 6, 1331–1335 (1999). https://doi.org/10.1038/sj.gt.3300944

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  • DOI: https://doi.org/10.1038/sj.gt.3300944

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