Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Hum Gene Ther. 2023 May;34(9-10):372-378. doi: 10.1089/hum.2023.026. Epub 2023 May 3.
Antisense oligonucleotide (ASO)-mediated exon skipping can restore the open reading frame of dystrophin transcripts for Duchenne muscular dystrophy (DMD) patients. This allows production of internally deleted dystrophin proteins as found in the later onset, less severely progressive Becker muscular dystrophy. At present, ASOs that induce exon skipping and dystrophin restoration are approved for the treatment of DMD by the regulatory agencies of the United States and Japan. However, approval was based on restoration of very small amounts of dystrophin and the approved ASOs apply to only a subset of patients. This expert perspective evaluates ways to improve ASO efficiency that are currently in or close to clinical trials, as well as ways to improve applicability of this mutation-specific approach.
反义寡核苷酸（ASO）介导的外显子跳跃可以恢复杜氏肌营养不良症（DMD）患者的肌营养不良蛋白转录本的开放阅读框。这使得可以产生在较晚发病、进展较慢的贝克肌营养不良症中发现的内部缺失的肌营养不良蛋白。目前，美国和日本的监管机构已批准 ASO 诱导外显子跳跃和肌营养不良蛋白恢复用于 DMD 的治疗。然而，批准是基于非常少量的肌营养不良蛋白的恢复，并且批准的 ASO 仅适用于患者的一部分。本专家观点评估了目前处于临床试验或接近临床试验的提高 ASO 效率的方法，以及提高这种突变特异性方法适用性的方法。
