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Differential expression and secretion of alpha 1 anti-trypsin between direct DNA injection and implantation of transfected myoblast

Gene Therapy volume 6, pages 1021–1029 (1999)Cite this article

Abstract

Muscle can be used for systemic delivery of non-muscle proteins. In order to investigate the relative effectiveness of direct DNA plasmid injection versus implantation of genetically modified myogenic cell lines, we have used the human alpha 1 anti-trypsin (α1AT) cDNA driven by either cytomegalovirus (CMV) or the muscle creatine kinase 3.3 kb (MCK) promoter in immunodeficient mice. We dem- onstrate that the implantation of transfected myoblasts stably expressing the human α1AT cDNA generates a more persistent production of α1AT than does direct intramuscular injection of the same construct as plasmid DNA. Moreover, immunohistological labelling of muscle sections implanted with myoblasts show that the newly formed muscle fibres are those containing the human protein.

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Acknowledgements

The authors would like to thank Dr Peter Strong for the P6 antibody, Jamie Morrison for technical assistance, Kim Wells for performing the CK assay and critical reading of the manuscript.

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Authors and Affiliations

  1. Muscle Cell Biology Group, MRC, Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Campus, London, UK

    G Bou-Gharios, Q L Lu, J E Morgan & T Partridge

  2. Department of Neuromuscular Diseases, Division of Neurosciences and Psychological Medicine, Gene Targetting Group, Imperial College School of Medicine, Charing Cross Campus, London, UK

    D J Wells

Authors
  1. G Bou-Gharios
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  2. D J Wells
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  3. Q L Lu
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  4. J E Morgan
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  5. T Partridge
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Bou-Gharios, G., Wells, D., Lu, Q. et al. Differential expression and secretion of alpha 1 anti-trypsin between direct DNA injection and implantation of transfected myoblast. Gene Ther 6, 1021–1029 (1999). https://doi.org/10.1038/sj.gt.3300933

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  • DOI: https://doi.org/10.1038/sj.gt.3300933

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