Duchenne型肌营养不良症（DMD）是一种致死性肌萎缩的X连锁隐性遗传病，由DMD基因突变导致抗肌萎缩蛋白（dystrophin）缺失而致病。基因治疗是目前研究热点。近年兴起的CRISPR/Cas9基因编辑技术可永久地编辑基因缺陷，并在DMD模型鼠的治疗取得了进展。但由于种属差异，是否能在体内有效编辑人的DMD基因，持续表达dystrophin尚不清楚。我们前期研究表明：人肌源性干细胞可在小鼠体内成肌分化，并长期嵌合生长。我们设想：如果将DMD患者的肌源性干细胞移植到免疫缺陷小鼠体内，构建人源化肌肉嵌合DMD模型鼠，再以腺相关病毒为载体的CRISPR/Cas9治疗模型鼠，极有可能使来自DMD患者的肌细胞的dystrophin能长期持续表达，肌细胞功能恢复。与此同时探讨CRISPR/Cas9体内编辑DMD的机制、效率和安全性。为CRISPR/Cas9治疗DMD的临床应用，提供重要的依据。

Duchenne Muscular Dystrophy (DMD) is a deadly X-linked recessive hereditary disease, which caused by the deficiency of dystrophin arising from mutations of DMD gene. Nowadays, gene therapy is the hotspot for the research of DMD. CRISPR/Cas9 could edit gene defects permanently, and have made progress on mdx mice. But if CRISPR/Cas9 could edit human DMD gene in vivo and restore dystrophin was still unknown. Our previous studies indicated that human-derived MDSCs could differentiate into muscle cells in mice. So we assumed that if we transplant DMD patients’ MDSCs to immunodeficient mice, build a humanized muscle-chimeric DMD model mice, and treat the model mice with AAV- CRISPR/Cas9. It is likely to restore dystrophin and function persistently in DMD derived muscle cells. Meanwhile, we could explore the mechanism, efficiency and security of CRISPR/Cas9 in DMD gene editing in vivo. This project could provide important basis for CRISPR/Cas9 in DMD clinical therapy.