Ragot T, Vincent N, Chafey P, Vigne E, Gilgenkrantz H, Couton D, Cartaud J, Briand P, Kaplan J C, Perricaudet M
URA 1301 CNRS, Institut Gustave Roussy, Villejuif, France.
Nature. 1993 Feb 18;361(6413):647-50. doi: 10.1038/361647a0.
Duchenne progressive muscular dystrophy is a lethal and common X-linked genetic disease caused by the absence of dystrophin, a 427K protein encoded by a 14 kilobase transcript. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin. Adenovirus is an efficient vector for in vivo expression of various foreign genes. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle.
杜兴氏进行性肌营养不良症是一种常见的致死性X连锁遗传病，由肌营养不良蛋白缺失所致，该蛋白是一种由14千碱基转录本编码的427K蛋白。已提出两种方法来纠正肌肉中的肌营养不良蛋白缺陷。第一种是成肌细胞移植疗法，使用来自正常供体的细胞，而第二种方法是直接将表达肌营养不良蛋白的重组质粒注射到肌肉中。腺病毒是一种在体内高效表达各种外源基因的载体。最近已证明，表达lac-Z报告基因的重组腺病毒能稳定感染许多小鼠组织，尤其是肌肉和心脏。我们测试了一种重组腺病毒的能力，该腺病毒含有由劳斯肉瘤病毒启动子驱动的6.3千碱基对贝克尔样肌营养不良蛋白互补DNA，在肌肉注射后，能在受感染的293细胞和C2成肌细胞以及mdx小鼠中指导“微型肌营养不良蛋白”的表达。我们在此报告，在体内，我们在注射肌肉高达50%的纤维中获得了肌膜免疫染色。
