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  • Inherited Disease
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Immune rejection of human dystrophin following intramuscular injections of naked DNA in mdx mice

Gene Therapy volume 7, pages 1447–1457 (2000)Cite this article

Abstract

Intramuscular administration of plasmid expressing full- length human dystrophin in dystrophin-deficient adult mdx mice resulted in humoral and weak specific T cell responses against the human dystrophin protein. Following plasmid injection, human dystrophin was detected in the injected muscles at 7 days, but decreased thereafter. Anti-dystrophin antibodies were found 21 days following plasmid injection, which coincided with transient myositis. This immune rejection prevented the mice from expressing human dystrophin after a second plasmid injection. No anti-DNA antibodies were found. Anti-dystrophin antibodies were seen in a smaller proportion of plasmid-injected dystrophin-competent C57BL/10 mice, suggesting that the immune rejection of dystrophin may be explained partially by species differences in the dystrophin protein.

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Acknowledgements

We are especially grateful to Professor George Dickson for his contribution to our research project. The authors thank Isabelle Renardet for providing purified plasmid DNA; Klaus Schughart, Head of Transgène's animal facility; Fabrice Augé, Grégory Amann, and David Bock for animal care; Virginie Nourtier, Gwenaelle Legoc, Doris Schmitt, and Karine Dott for technical assistance; and Dominic Wells for helpful discussions. This work was supported by the Association Française contre les Myopathies (AFM).

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  1. Transgène S.A., 11 rue de Molsheim, Strasbourg Cedex, 67082, France

    S Braun, C Thioudellet, P Rodriguez, D Ali-Hadji, F Perraud, N Accart, J-M Balloul, C Halluard, B Acres, B Cavallini & A Pavirani

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Braun, S., Thioudellet, C., Rodriguez, P. et al. Immune rejection of human dystrophin following intramuscular injections of naked DNA in mdx mice. Gene Ther 7, 1447–1457 (2000). https://doi.org/10.1038/sj.gt.3301261

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