脊髓小脑共济失调3型是一种基因重复序列异常扩增导致的难治性疾病，严重影响患者生活及生存。我们前期研究发现：应用CRISPR/Cas9技术可修复基因突变患者iPS细胞的错误扩增，为自体细胞移植治疗该类疾病提供了方向。目前尚无基因修复后干细胞移植治疗SCA3的安全性及有效性的研究报道。在本课题中，我们已建立SCA3患者来源的ips细胞，应用更优化的基因编辑策略对iPS细胞进行了基因修复，培育了SCA3小鼠，拟将修复后的iPS细胞分化为神经干细胞后移植入SCA3小鼠体内，通过行为学评估、神经病理学改变、神经保护因子、炎症因子及相关免疫通路蛋白改变，探讨细胞移植治疗的安全性、有效性及相关机制，为基因修复后SCA3患者特异干细胞自体移植治疗提供临床前研究的理论依据，进而推动基因编辑技术与干细胞移植在神经遗传性疾病治疗方面的应用及临床转化。

Spinocerebellar ataxia type 3 (SCA3) is a refractory disease caused by abnormal amplification of gene repeats and impairs the quality of life and survival of patients seriously. Our previous study found that the application of CRISPR/Cas9 technology could correct the influence of the pathogenic gene mutation of iPSCs, which could be a new therapy for that cell transplantation cure this kind of disease. However, there are no reports evaluating the safety and effectiveness of genome-edited stem cell transplantation to therapy SCA3. In our study, we have generated normal and SCA3 patient-derived iPSCs and neural stem cells, performed gene repair in iPS cells using a more optimized gene editing strategy and cultured SCA3 mice. We intend to induce the repaired iPSCs into neural stem cells, then transplant the cells into SCA3 model mice. Then explore the safety, efficacy and related mechanisms of cell transplantation through behavioral assessment, neuropathological changes, changes in neuroprotective factors, inflammatory factors and related immune pathway proteins. Besides, provide a theoretical basis for preclinical studies on the treatment of SCA3 patients with genome-repaired SCA3 patient-derived stem cells transplantation. Furthermore, it will promote the application and clinical transformation of gene editing technology and stem cell transplantation in the treatment of SCA3 and other inherited neurodegenerative diseases.