Wilton S D, Fletcher S
Experimental Molecular Medicine Group, Centre for Neuromuscular and Neurological Disorders, University of Western Australia.
Acta Myol. 2005 Dec;24(3):222-9.
Antisense oligonucleotide induced exon skipping has recently emerged as a potential therapy to by-pass the consequences of many, but not all dystrophin mutations that lead to Duchenne muscular dystrophy. Targeted removal of one or more exons, to restore a disrupted reading frame, or omit a nonsense mutation, could lessen the consequences of an estimated 80% of dystrophin gene mutations. Promising in vitro and in vivo experiments in animal models of dystrophinopathies, as well as demonstration of induced exon skipping in cultured human myogenic cells have prompted considerable enthusiasm. Furthermore, advances in antisense oligonucleotide chemistries have resulted in the development of more stable and less toxic compounds, some of which are currently in Phase III clinical trials for selected antiviral applications. This review will summarize developments in induced exon skipping that have paved the way to clinical trials and some of the challenges and possible limitations.
反义寡核苷酸诱导的外显子跳跃最近已成为一种潜在的治疗方法，用于绕过许多（但不是全部）导致杜氏肌营养不良症的肌营养不良蛋白突变的后果。靶向去除一个或多个外显子，以恢复中断的阅读框或省略无义突变，可能会减轻估计80%的肌营养不良蛋白基因突变的后果。在肌营养不良症动物模型中进行的有前景的体外和体内实验，以及在培养的人成肌细胞中诱导外显子跳跃的证明，引发了相当大的热情。此外，反义寡核苷酸化学的进展导致了更稳定、毒性更小的化合物的开发，其中一些目前正处于针对选定抗病毒应用的III期临床试验阶段。本综述将总结诱导外显子跳跃方面的进展，这些进展为临床试验铺平了道路，以及一些挑战和可能的局限性。
