UTMD介导基于CRISPR/Cas9技术的靶向SEPS1基因敲除实现桥本氏甲状腺炎基因治疗的研究

Hashimoto's thyroiditis（HT）is the most common and frequently-occurring disease in clinic. However, there is rare effective early treatment approach to cure this disease. Our previous findings provide supporting evidence which suggested potential roles of the SEPS1 gene in the pathogenesis and etiology of HT. On the basis of the pathogenesis and clinical research progress of HT, we designed CRISPR/Cas9 lentiviral vectors to induce cleavage of the rat endogenous SPES1 loci in order to generate the SEPS1 gene fixed-point knockout. After generating rat HT model, integrin monoclonal antibody marked targeted microbubbles carrying CRISPR/Cas9 lentiviral vectors is targeted blasting in thyroid gland using ultrasound-targeted microbubble destruction technique. Repair effects of SEPS1 gene knockout on HT are evaluated by observing the SEPS1 expression, inflammatory factor expression, secreting hormones expression as well as pathological histology changes of animal models. Our studies may provide a solid experimental basis and theoretical preparation for early treatment of HT.

桥本氏甲状腺炎（HT）是临床常见病、多发病。目前缺乏有效的早期治疗方法。申请人通过前期基因多态性与疾病关联分析研究创新性的发现，人类硒蛋白相关基因SEPS1与中国汉族人群HT的发病具有高度的强关联性。本课题针对HT疾病发病机制的临床研究进展及申请人前期研究基础，以HT靶向基因治疗为切入点，创新性的利用CRISPR/Cas9双载体慢病毒基因敲除技术实现SEPS1基因定点敲除，利用UTMD技术靶向爆破的特点，在甲状腺局部靶向爆破整合素单抗修饰的负载具有SEPS1基因敲除功能的CRISPR/Cas9双载体慢病毒靶向微泡，通过体内外实验评价SEPS1基因敲除对HT疾病的治疗作用，为HT早期治疗提供坚实的实验基础和理论准备。

桥本氏甲状腺炎(HT)是临床常见病、多发病。目前缺乏有效的早期治疗方法。申请人通过前期基因多态性与疾病关联分析研究创新性的发现，人类硒蛋白相关基因SEPS1与中国汉族人群HT的发病具有高度的强关联性。本课题针对HT疾病发病机制的临床研究进展及申请人前期研究基础，以HT靶向基因治疗为切入点，创新性的通过实现SEPS1基因干扰，利用UTMD技术靶向爆破的特点，在甲状腺局部靶向爆破负载具有SEPS1基因干扰功能的干扰病毒靶向微泡，通过体内外实验证实了SEPS1基因敲除对HT疾病的治疗作用，为HT早期治疗提供坚实的实验基础和理论准备。