Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Gene. 2023 May 30;867:147358. doi: 10.1016/j.gene.2023.147358. Epub 2023 Mar 11.
Duchenne muscular dystrophy (DMD) is caused by the dystrophin gene mutations and is one of the most common and lethal human hereditary disorders. A novel therapeutic approach using CRISPR technology has gained attention in the treatment of DMD. Gene replacement strategies are being proposed as a promising therapeutic option to compensate the loss of function mutations. Although, the large size of the dystrophin gene and the limitations of the existing gene replacement approach, could mean the gene delivery of shortened versions of dystrophin such as midystrophin and microdystrophins. There are also other approaches: including Targeted removal of dystrophin exons to restore the reading-frame; Dual sgRNA-directed DMD exon deletion, CRISPR-SKIP strategy; reframing of dystrophin using Prime Editing technology; exon removal using twin prime technology; TransCRISTI technology to targeted exon integration into dystrophin gene. Here we provide an overview of recent progresses in dystrophin gene editing using updated versions of CRISPR to introduce novel opportunities in DMD gene therapy. Overall, the novel CRISPR based technologies are improving and expanding to allow the application of more precise gene editing for the treatment of DMD.
杜氏肌营养不良症（DMD）是由肌营养不良蛋白基因突变引起的，是最常见和最致命的人类遗传性疾病之一。使用 CRISPR 技术的新型治疗方法在 DMD 的治疗中引起了关注。基因替换策略被提出作为一种有前途的治疗选择，以补偿功能缺失突变。然而，肌营养不良蛋白基因的大小和现有基因替换方法的局限性，可能意味着可以输送缩短的肌营养不良蛋白，如中肌营养不良蛋白和微肌营养不良蛋白。还有其他方法：包括靶向去除肌营养不良蛋白外显子以恢复阅读框；双 sgRNA 指导的 DMD 外显子缺失，CRISPR-SKIP 策略；使用 Prime Editing 技术重新构建肌营养不良蛋白；使用双引物技术去除外显子；TransCRISTI 技术将靶向外显子整合到肌营养不良蛋白基因中。在这里，我们提供了使用更新版本的 CRISPR 进行肌营养不良蛋白基因编辑的最新进展概述，为 DMD 基因治疗带来了新的机会。总的来说，新型基于 CRISPR 的技术正在不断改进和扩展，以允许更精确的基因编辑应用于 DMD 的治疗。
