For many neuromuscular disorders, including Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy, the genetic causes are well known. Gene therapy holds promise for the treatment of these monogenic neuromuscular diseases, and many such therapies have made substantial strides toward clinical translation. Recently, genome engineering tools, including targeted gene editing and gene regulation, have become available to correct the underlying genetic mutations that cause these diseases. In particular, meganucleases, zinc finger nucleases, TALENs, and the CRISPR–Cas9 system have been harnessed to make targeted and specific modifications to the genome. However, for most gene therapy applications, including genome engineering, gene delivery remains the primary hurdle to clinical translation. In preclinical models, genome engineering tools have been delivered via gene-modified cells or by non-viral or viral vectors to correct a diverse array of genetic diseases. In light of the positive results of these studies, genome engineering therapies are being enthusiastically explored for several genetic neuromuscular disorders. This Review summarizes the genome engineering strategies that are currently under preclinical evaluation for the treatment of degenerative neuromuscular disorders, with a focus on the molecular tools that show the greatest potential for clinical translation of these therapies.

对于许多神经肌肉疾病，包括杜兴氏肌营养不良症，脊髓性肌萎缩症和强直性肌营养不良症，其遗传原因是众所周知的。基因疗法有望治疗这些单基因神经肌肉疾病，许多这样的疗法已在临床翻译方面取得了长足的进步。最近，基因组工程工具，包括靶向基因编辑和基因调控，已经可以用来纠正引起这些疾病的潜在基因突变。特别是，已经利用大范围核酸酶，锌指核酸酶，TALEN和CRISPR–Cas9系统对基因组进行靶向和特异性修饰。然而，对于包括基因组工程在内的大多数基因治疗应用而言，基因传递仍然是临床翻译的主要障碍。在临床前模型中，基因组工程工具已通过基因修饰细胞或非病毒或病毒载体提供，以纠正多种遗传疾病。鉴于这些研究的积极结果，人们正在积极地探索基因组工程疗法来治疗几种遗传性神经肌肉疾病。这篇综述总结了目前正在临床前评估的用于治疗变性神经肌肉疾病的基因组工程策略，重点是显示出这些疗法的临床翻译潜力最大的分子工具。人们正在积极地探索基因组工程疗法来治疗几种遗传性神经肌肉疾病。这篇综述总结了目前正在临床前评估的用于治疗变性神经肌肉疾病的基因组工程策略，重点是显示出这些疗法的临床翻译潜力最大的分子工具。人们正在积极地探索基因组工程疗法来治疗几种遗传性神经肌肉疾病。这篇综述总结了目前正在临床前评估的用于治疗变性神经肌肉疾病的基因组工程策略，重点是显示出这些疗法的临床翻译潜力最大的分子工具。