Duchenne型肌营养不良症（Duchenne muscular dystrophy，DMD）是由DMD基因突变所引起的一种致死性单基因遗传病，尚无有效治疗手段。以CRISPR/Cas9基因编辑为代表的基因治疗是最有希望改善DMD预后的方法之一。然而，目前对DMD的基因编辑研究多集中于编码杆状区的片段，对与dystrophin蛋白功能密切相关的N端ABD-1区域的研究尚不充分，且没有理想的研究模型。前期我们利用CRISPR/Cas9技术，敲除了c57小鼠DMD基因7-8号外显子，构建了一种新型的ABD-1突变的DMD模型鼠（mdxΔE7-8）。以此模型为基础，通过以AAV9为载体的CRISPR/Cas9体系治疗mdxΔE7-8小鼠，探究针对ABD-1突变体的不同基因编辑策略对小鼠肌肉功能的影响及其机制，为利用CRISPR/Cas9治疗DMD基因ABD-1突变打下重要基础。

Duchenne muscular dystrophy（DMD）is a fatal monogenic disease caused by mutations in DMD gene, which is currently untreatable. Gene therapy such as CRISPR/Cas9, is one of the most promising way to improve the prognosis of DMD. The gene editing researches involving DMD gene mainly focused on the fragment encoding rod domain. There were few researches involving the ABD-1 domain of N terminal which is closely associated with the function of dystrophin, besides there was no ideal model for the research of ABD-1. Previously, we knocked out exon7 and exon8 of DMD gene in c57 mice by using CRISPR/Cas9, and constructed a novel ABD-1 mutant DMD model mice(mdxΔE7-8). Based this model, we attempt to treat the mdxΔE7-8 mice by using AAV9-CRISPR/Cas9, and explore the influence of the different gene editing strategies on the muscle function of the mice, and the mechanism behind it. This research will lay a foundation for the CRISPR/Cas9-mediated treatment for ABD-1 mutant.