Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Genes (Basel). 2022 Jan 28;13(2):257. doi: 10.3390/genes13020257.
Duchenne muscular dystrophy (DMD) is a fatal genetic disease affecting children that is caused by a mutation in the gene encoding for dystrophin. In the absence of functional dystrophin, patients experience progressive muscle deterioration, leaving them wheelchair-bound by age 12 and with few patients surviving beyond their third decade of life as the disease advances and causes cardiac and respiratory difficulties. In recent years, an increasing number of antisense and gene therapies have been studied for the treatment of muscular dystrophy; however, few of these therapies focus on treating mutations arising in the N-terminal encoding region of the dystrophin gene. This review summarizes the current state of development of N-terminal antisense and gene therapies for DMD, mainly focusing on exon-skipping therapy for duplications and deletions, as well as microdystrophin therapy.
杜氏肌营养不良症（DMD）是一种致命的遗传性疾病，影响儿童，由编码肌营养不良蛋白的基因突变引起。在缺乏功能性肌营养不良蛋白的情况下，患者会经历进行性肌肉恶化，导致他们在 12 岁时需要使用轮椅，并且由于疾病的进展导致心脏和呼吸问题，很少有患者能够活到第三个十年。近年来，越来越多的反义核酸和基因疗法被研究用于治疗肌肉营养不良症；然而，这些疗法中很少有针对肌营养不良蛋白基因 N 端编码区突变的治疗方法。本文总结了目前针对 DMD 的 N 端反义核酸和基因治疗的发展状况，主要集中在针对重复和缺失的外显子跳跃治疗以及微小肌营养不良蛋白治疗上。
