ABSTRACT

Introduction

Exon skipping compounds restoring the dystrophin transcript reading frame have received regulatory approval for Duchenne muscular dystrophy (DMD). Recently, focus shifted to developing compounds to skip additional exons, improving delivery to skeletal muscle, and to genome editing, to restore the reading frame on DNA level.

Areas covered

We outline developments for reading frame restoring approaches, challenges of mutation specificity, and optimizing delivery. Also, we highlight ongoing efforts to better detect exon skipping therapeutic effects in clinical trials. Searches on relevant terms were performed, focusing on recent publications (<3 years).

Expert opinion

Currently, 3 AONS are approved. Whether dystrophin levels are sufficient to slowdown disease progression needs to be confirmed. Enhancing AON uptake by muscles is currently under investigation. Gene editing is an alternative, but one that involves practical and ethical concerns. Given the field’s momentum, we believe the efficiency of frame-restoring approaches will improve.

中文翻译：

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杜氏肌营养不良症阅读框恢复治疗方法的进展

摘要

介绍

恢复肌营养不良蛋白转录阅读框的外显子跳跃化合物已获得杜氏肌营养不良症 (DMD) 的监管批准。最近，重点转移到开发化合物以跳过额外的外显子，改善向骨骼肌的传递，以及基因组编辑，以恢复 DNA 水平的阅读框。

涵盖的领域

我们概述了阅读框恢复方法、突变特异性挑战和优化传递的发展。此外，我们强调了在临床试验中更好地检测外显子跳跃治疗效果的持续努力。对相关术语进行了搜索，重点是最近的出版物（<3 年）。

专家意见

目前，批准了 3 个 AONS。肌营养不良蛋白水平是否足以减缓疾病进展需要得到证实。目前正在研究增强肌肉对 AON 的吸收。基因编辑是另一种选择，但涉及实际和伦理问题。鉴于该领域的发展势头，我们相信帧恢复方法的效率将会提高。