Wells K E, Fletcher S, Mann C J, Wilton S D, Wells D J
Department of Neuromuscular Diseases, Imperial College London, Charing Cross Hospital, W6 8RP London, UK.
FEBS Lett. 2003 Sep 25;552(2-3):145-9. doi: 10.1016/s0014-5793(03)00904-9.
The use of antisense oligonucleotides (AOs) to induce exon skipping leading to generation of an in-frame dystrophin protein product could be of benefit in around 70% of Duchenne muscular dystrophy patients. We describe the use of hyaluronidase enhanced electrotransfer to deliver uncomplexed 2'-O-methyl modified phosphorothioate AO to adult dystrophic mouse muscle, resulting in dystrophin expression in 20-30% of fibres in tibialis anterior muscle after a single injection. Although expression was transient, many of the corrected fibres initially showed levels of dystrophin expression well above the 20% of endogenous previously shown to be necessary for phenotypic correction of the dystrophic phenotype.
使用反义寡核苷酸（AO）诱导外显子跳跃从而产生读码框内的肌营养不良蛋白产物，这可能使约70%的杜氏肌营养不良患者受益。我们描述了利用透明质酸酶增强电转染将未复合的2'-O-甲基修饰硫代磷酸酯AO递送至成年营养不良小鼠肌肉，单次注射后，胫前肌中20%-30%的肌纤维出现了肌营养不良蛋白表达。尽管表达是短暂的，但许多校正后的肌纤维最初显示出的肌营养不良蛋白表达水平远高于先前表明的对营养不良表型进行表型校正所需的内源性水平的20%。
