Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping
Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping
复制标题
DOI：
10.1126/science.1104297
复制
发表时间：
2004-12-03
期刊：
影响因子：
56.9
通讯作者：
Danos, O
中科院分区：
文献类型：
--
作者：
Goyenvalle, A;Vulin, A;Danos, O
肌营养不良蛋白基因中的大多数突变都会导致 mRNA 发生移码或停止，并与严重杜氏肌营养不良症相关。低频率自然发生的外显子跳跃有时会消除突变并导致产生拯救的蛋白质。我们通过单次施用表达与修饰的 U7 小核 RNA 连接的反义序列的 AAV 载体，实现了持久的外显子跳跃，去除了 mdx 小鼠肌营养不良蛋白信使 mRNA 上的突变外显子。我们报告了整个肌肉群在生理水平上持续产生功能性肌营养不良蛋白以及肌营养不良症的纠正。
Most mutations in the, dystrophin gene create a frameshift or a stop in the mRNA and are associated with severe Duchenne muscular dystrophy. Exon skipping that naturally occurs at low frequency sometimes eliminates the mutation and leads to the production of a rescued protein. We have achieved persistent exon skipping that removes the mutated exon on the dystrophin messenger mRNA of the mdx mouse, by a single administration of an AAV vector expressing antisense sequences linked to a modified U7 small nuclear RNA. We report the sustained production of functional dystrophin at physiological levels in entire groups of muscles and the correction of the muscular dystrophy.