AAV2衣壳蛋白工程化改造对提升帕金森病基因治疗疗效的研究进展  

Research progress of AAV2 capsid protein engineering modification to enhance the efficacy of parkinson’s disease gene therapy

作　　者：梁瑞 黄南渠 罗勇 Liang Rui;Huang Nanqu;Luo Yong(Department of Neurology;National Drug Clinical Trial Institution,the Third Affiliated Hospital of Zunyi Medical University,First People’s Hospital of Zunyi,Zunyi Guizhou 563000,China)

机构地区：[1]遵义医科大学第三附属医院,遵义市第一人民医院神经内科,贵州遵义563000 [2]遵义医科大学第三附属医院,遵义市第一人民医院药物临床试验机构办公室,贵州遵义563000

出　　处：《遵义医科大学学报》2023年第3期319-326,共8页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:82260774)。

摘　　要：帕金森病(PD)是一种以黑质致密部多巴胺能(DA)神经元进行性丢失为主要特征的神经退行性疾病,目前临床上主要以药物、康复及脑深部电刺激等治疗方式为主,但均不能阻止病情进展。近年来,基因治疗在PD的临床前及临床研究中,已初步显示出广阔前景。腺相关病毒2型(AAV2)因其安全性,已广泛用于PD疾病模型构建并作为基因治疗的载体,目前相关研究虽取得一定进展,但仍有许多不足,包括AAV2对DA神经元特定细胞特异性较低、体内血清中和抗体(Nab)限制病毒有效分布、动物模型构建及临床转换困难等。基于此,本文将探讨AAV2衣壳蛋白工程化改造对提升PD基因治疗的疗效做一综述。The progressive loss of Dopamine(DA)neurons in substantia nigra compacta(SNc)is regarded as the key pathological character of Parkinson's disease(PD).However,drugs,rehabilitation,and deep brain stimulation can’t decline the clinical progression of PD.Currently,gene therapy has presented broad prospects in preclinical and clinical research.Adeno-associated virus 2(AAV2)has been widely used as a vector for PD gene therapy and disease model construction due to its safety.Although some progression has been made at present,there are still many shortcomings,include AAV2 has low specificity to specific cells of DA neurons,the existence of neutralizing antibodies in serum hindering the effective distribution of viruses,and the difficult of Animal model construction,as well as the clinical conversion.Based on these issues,this paper is focused on the progression of engineering transformation of AAV2 capsid protein which improves the efficacy of PD gene therapy.

关 键 词：腺相关病毒 腺相关病毒2型 衣壳工程 病毒载体 基因治疗 帕金森病 

分 类 号：Q812[生物学—生物工程] R742.5[医药卫生—神经病学与精神病学]