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Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs

Naturevolume 352pages815818 (1991) | Download Citation

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Abstract

DUCHENNE'S muscular dystrophy (DMD), which affects one in 3,500 males, causes progressive myopathy of skeletal and cardiac muscles and premature death1. One approach to treatment would be to introduce the normal dystrophin gene into diseased muscle cells. When pure plasmid DNA is injected into rodent skeletal2 or cardiac muscle3–5, the cells express reporter genes. We now show that a 12-kilobase full-length human dystrophin complemen-tary DNA gene and a 6.3-kilobase Becker-like gene6 can be expressed in cultured cells and in vivo. When the human dystrophin expression plasmids are injected intramuscularly into dystrophin-deficient mdx mice, the human dystrophin proteins are present in the cytoplasm and sarcolemma of 1% of the myofibres. Myofibres expressing human dystrophin contain an increased proportion of peripheral nuclei. The results indicate that transfer of the dystrophin gene into the myofibres of DMD patients could be beneficial, but a larger number of genetically modified myofibres will be necessary for clinical efficacy.

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Author information

Author notes

    • Gyula Acsadi

    Present address: Department of Pediatrics, University Medical School of Pecs, H-7623, Hungary

Affiliations

  1. Departments of Pediatrics and Medical Genetics, Waisman Center, University of Wisconsin, Madison, Wisconsin, 53706, USA

    • Gyula Acsadi
    • , Agnes Jani
    •  & Jon A. Wolff
  2. Department of Experimental Pathology, UMDS, Guy's Hospital, London Bridge, London, SE19RT, UK

    • George Dickson
    •  & Frank S. Walsh
  3. Molecular Genetics Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, 0X3 9DU, UK

    • Donald R. Love
    • , Asitha Gurusinghe
    •  & Kay E. Davies

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https://doi.org/10.1038/352815a0

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