1 Department of Molecular Microbiology, College of Veterinary Medicine, The University of Missouri, Columbia.
2 National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland.
Hum Gene Ther. 2019 May;30(5):535-543. doi: 10.1089/hum.2018.243. Epub 2019 Feb 26.
Clustered regularly interspaced short palindromic repeats (CRISPR) editing is being considered as a potential gene repair therapy to treat Duchenne muscular dystrophy, a dystrophin-deficient lethal muscle disease affecting all muscles in the body. A recent preliminary study from the Olson laboratory (Amoasii . Science 2018;362:89-91) showed robust dystrophin restoration in a canine Duchenne muscular dystrophy model following intramuscular or intravenous delivery of the CRISPR editing machinery by adeno-associated virus serotype 9. Despite the limitation of the small sample size, short study duration, and the lack of muscle function data, the Olson lab findings have provided important proof of principle for scaling up CRISPR therapy from rodents to large mammals. Future large-scale, long-term, and comprehensive studies are warranted to establish the safety and efficacy of CRISPR editing therapy in large mammals.
成簇规律间隔短回文重复（CRISPR）编辑被认为是一种潜在的基因修复疗法，可用于治疗杜氏肌营养不良症，这是一种肌营养不良蛋白缺乏的致命肌肉疾病，会影响全身所有肌肉。奥尔森实验室（Amoasii）最近的一项初步研究（Science 2018;362:89-91）表明，在犬类杜氏肌营养不良症模型中，通过腺相关病毒血清型 9 肌内或静脉内递送 CRISPR 编辑机制，可实现强有力的肌营养不良蛋白恢复。尽管存在样本量小、研究时间短以及缺乏肌肉功能数据等局限性，但奥尔森实验室的研究结果为从啮齿动物到大型哺乳动物扩大 CRISPR 治疗提供了重要的原理证明。未来需要进行大规模、长期和全面的研究，以确定 CRISPR 编辑疗法在大型哺乳动物中的安全性和疗效。
