rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice
rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice
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DOI：
10.1038/nm1439
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发表时间：
2006-07-01
期刊：
影响因子：
82.9
通讯作者：
Chamberlain, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Gregorevic, Paul;Allen, James M.;Chamberlain, Jeffrey S.
携带营养不良蛋白和营养不良蛋白基因突变的小鼠由于严重的肌肉萎缩症而过早死亡。在这里，我们表明，血管内给予携带微肌营养不良蛋白基因的重组腺相关病毒（rAAV）载体，可以恢复这些小鼠呼吸、心脏和肢体肌肉组织中肌营养不良蛋白的表达，显著减少骨骼肌病理并延长寿命。这些发现表明，rAAV载体介导的全身基因转移可能有助于治疗严重的神经肌肉疾病，如杜氏肌营养不良症。
Mice carrying mutations in both the dystrophin and utrophin genes die prematurely as a consequence of severe muscular dystrophy. Here, we show that intravascular administration of recombinant adeno-associated viral (rAAV) vectors carrying a microdystrophin gene restores expression of dystrophin in the respiratory, cardiac and limb musculature of these mice, considerably reducing skeletal muscle pathology and extending lifespan. These findings suggest rAAV vector-mediated systemic gene transfer may be useful for treatment of serious neuromuscular disorders such as Duchenne muscular dystrophy.