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

被引:45
作者
Braun, S [1 ]
Thioudellet, C [1 ]
Rodriguez, P [1 ]
Ali-Hadji, D [1 ]
Perraud, F [1 ]
Accart, N [1 ]
Balloul, JM [1 ]
Halluard, C [1 ]
Acres, B [1 ]
Cavallini, B [1 ]
Pavirani, A [1 ]
机构
[1] Transgene SA, F-67082 Strasbourg, France
关键词
dystrophin; mdx; immunology; Duchenne; plasmid; gene therapy;
D O I
10.1038/sj.gt.3301261
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1447 / 1457
页数:11
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