Immune rejection of human dystrophin following intramuscular injections of naked DNA in mdx mice |
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Authors: | Braun S Thioudellet C Rodriguez P Ali-Hadji D Perraud F Accart N Balloul J M Halluard C Acres B Cavallini B Pavirani A |
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Institution: | Transgène S.A., Strasbourg, France. |
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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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