EFFICIENT ADENOVIRUS-MEDIATED TRANSFER OF A HUMAN MINIDYSTROPHIN GENE TO SKELETAL-MUSCLE OF MDX MICE
EFFICIENT ADENOVIRUS-MEDIATED TRANSFER OF A HUMAN MINIDYSTROPHIN GENE TO SKELETAL-MUSCLE OF MDX MICE
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DOI：
10.1038/361647a0
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发表时间：
1993-02-18
期刊：
影响因子：
64.8
通讯作者：
KAHN, A
中科院分区：
文献类型：
--
作者：
RAGOT, T;VINCENT, N;KAHN, A
DUCHENNE进行性肌营养不良症是一种致命的常见的x连锁遗传病1，由缺乏营养不良蛋白2,3引起，营养不良蛋白2,3是一种由14千碱基转录编码的427K蛋白。已经提出了两种方法来纠正肌肉中的肌营养不良蛋白缺乏。第一种是成肌细胞转移疗法，使用来自正常供体的细胞5-7，而第二种是直接在肌肉内注射表达肌营养不良蛋白8的重组质粒。腺病毒是多种外源基因在体内表达的有效载体9-13。最近有研究表明，一种表达lac-Z报告基因的重组腺病毒可以稳定地感染许多小鼠组织，特别是肌肉和心脏12,13。我们已经测试了一种重组腺病毒的能力，该病毒含有6.3千碱基对的贝氏样肌营养不良蛋白互补DNA14，由劳斯肉瘤病毒启动子驱动，在感染的293细胞和C2成肌细胞以及mdx小鼠中，肌肉注射后指导‘minidystrophin’的表达。我们在这里报告，在体内，我们已经获得了肌上皮免疫染色高达50%的纤维注射肌肉。
DUCHENNE progressive muscular dystrophy is a lethal and common X-linked genetic disease1 caused by the absence of dystrophin2,3, a 427K protein encoded by a 14 kilobase transcript4. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors5-7, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin8. Adenovirus is an efficient vector for in vivo expression of various foreign genes9-13. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart12,13. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA14 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 mouse15,16, 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.