Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology
Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology
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DOI：
10.1038/nm1345
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发表时间：
2006-02-01
期刊：
影响因子：
82.9
通讯作者：
Lu, QL
中科院分区：
文献类型：
--
作者：
Alter, J;Lou, F;Lu, QL
对于大多数Duchenne肌营养不良症（DMD）突变，反义寡核苷酸（AON）介导的外显子跳跃具有恢复功能蛋白的潜力。在这里，我们表明，每周静脉注射吗啉代磷酰二胺（吗啉代）AON诱导表达的功能水平的肌营养不良的mdx小鼠全身骨骼肌的肌营养不良蛋白，从而改善肌肉功能。虽然肌营养不良蛋白的表达水平在肌肉之间有很大差异，但反义治疗可能为大多数DMD患者的治疗提供了现实的希望。
For the majority of Duchenne muscular dystrophy (DMD) mutations, antisense oligonucleotide (AON)-mediated exon skipping has the potential to restore a functional protein. Here we show that weekly intravenous injections of morpholino phosphorodiamidate (morpholino) AONs induce expression of functional levels of dystrophin in body-wide skeletal muscles of the dystrophic mdx mouse, with resulting improvement in muscle function. Although the level of dystrophin expression achieved varies considerably between muscles, antisense therapy may provide a realistic hope for the treatment of a majority of individuals with DMD.