Dong Qi-Chao, Chen Hui-Min, Jin Xin
Medical School of Shaoxing University, Shaoxing, Zhejiang 312000, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2018 Aug;20(8):691-696. doi: 10.7499/j.issn.1008-8830.2018.08.017.
Duchenne muscular dystrophy (DMD) is an X-linked recessive hereditary disease caused by mutations in the DMD gene that encodes dystrophin. It is characterized by progressive muscle weakness and degeneration of skeletal muscle and myocardium due to the absence of dystrophin. The disease often occurs at the age of 2-5 years, and most children may die of heart failure or respiratory insufficiency at the age of around 20 years. At present, supportive therapy is often used in clinical practice to improve symptoms, but this cannot improve the outcome of this disease. The development of gene therapy brings new hope to the cure of this disease. This article summarizes gene replacement therapy for DMD, including the research advances in DMD gene transduction technology mediated by adeno-associated virus, utrophin protein upregulation technology, and clustered regularly interspaced short palindromic repeat gene editing technology, and reviews the recommendations to solve the issues of adeno-associated viral load, long-term effective expression of transgenic products, and utrophin protein expression, in order to provide a reference for further research.
杜兴氏肌肉营养不良症(DMD)是一种X连锁隐性遗传性疾病,由编码抗肌萎缩蛋白的DMD基因突变引起。其特征是由于缺乏抗肌萎缩蛋白,导致进行性肌肉无力以及骨骼肌和心肌退化。该疾病通常在2至5岁时发病,大多数患儿可能在20岁左右死于心力衰竭或呼吸功能不全。目前,临床实践中常采用支持性疗法来改善症状,但这并不能改善该疾病的预后。基因治疗的发展为治愈这种疾病带来了新希望。本文总结了DMD的基因替代疗法,包括腺相关病毒介导的DMD基因转导技术、肌营养蛋白上调技术和成簇规律间隔短回文重复序列基因编辑技术的研究进展,并对解决腺相关病毒载量、转基因产物长期有效表达以及肌营养蛋白表达等问题的建议进行了综述,以期为进一步研究提供参考。