School of Biological Sciences, Royal Holloway - University of London, Egham, Surrey TW20 0EX, United Kingdom.
Neuromuscul Disord. 2010 Feb;20(2):102-10. doi: 10.1016/j.nmd.2009.10.013. Epub 2010 Jan 15.
Duchenne muscular dystrophy (DMD) is caused by the lack of functional dystrophin protein, most commonly as a result of a range of out-of-frame mutations in the DMD gene. Modulation of pre-mRNA splicing with antisense oligonucleotides (AOs) to restore the reading frame has been demonstrated in vitro and in vivo, such that truncated but functional dystrophin is expressed. AO-induced skipping of exon 51 of the DMD gene, which could treat 13% of DMD patients, has now progressed to clinical trials. We describe here the methodical, cooperative comparison, in vitro (in DMD cells) and in vivo (in a transgenic mouse expressing human dystrophin), of 24 AOs of the phosphorodiamidate morpholino oligomer (PMO) chemistry designed to target exon 53 of the DMD gene, skipping of which could be potentially applicable to 8% of patients. A number of the PMOs tested should be considered worthy of development for clinical trial.
杜氏肌营养不良症（DMD）是由于缺乏功能性肌营养不良蛋白引起的，最常见的原因是 DMD 基因突变导致移码。反义寡核苷酸（AOs）可调节前体 mRNA 的剪接，恢复读框，从而表达截断但有功能的肌营养不良蛋白。在体外和体内均已证实 AO 诱导 DMD 基因外显子 51 的跳跃，可治疗 13%的 DMD 患者，现已进入临床试验阶段。我们在此描述了针对 DMD 基因外显子 53 的 24 种磷酰胺二酯修饰的吗啉代寡聚物（PMO）化学反义寡核苷酸的方法学、合作性比较，其跳跃可能适用于 8%的患者。其中一些 PMO 值得进一步开发用于临床试验。
