新型肌肉高效亲和AAV血清型的开发  

Generation of a Novel Muscle-Tropic AAV Serotype

作　　者：陈颖 吴佳梅 凌菲香 曾步兵[1] 郑静[1] 吴侠 赵锴 肖啸 CHEN Ying;WU Jiamei;LING Feixiang;ZENG Bubing;ZHENG Jing;WU Xia;ZHAO Kai;XIAO Xiao(School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学药学院,上海200237

出　　处：《华东理工大学学报（自然科学版）》2022年第1期51-58,共8页Journal of East China University of Science and Technology

基　　金：中央高校基本科研业务费专项资金赞助。

摘　　要：通过在AAV5衣壳的N573后插入一个寡肽PGPSPAD生成了一种改良的AAV血清型,称为AAVc1,它在体外和体内均表现出比AAV5、AAV8和AAV9更好的肌肉感染性;恒河猴血清中针对AAVc1的中和抗体(Neutralizing antibodies,Nabs)滴度低于AAV9,这表明针对AAVc1的中和抗体的免疫应答低于AAV9。结果表明,新型血清型AAVc1应用到AAV基因治疗中优于野生型AAV血清型。The paper generated a modified AAV serotype,named AAVc1,by inserting an oligopeptide PGPSPAD after N573 of the AAV5 capsid,which exhibited better muscle tropism than AAV5,8 and 9 both in vitro and in vivo.The number of green fluorescence protein(GFP)positive C2C12 myoblast cells in AAVc1 group was 25%higher than AAV9 group,almost twice the AAV8 group and three times of the AAV5 group.The percentage of both type I and type II skeletal muscle fibers infected by AAVc1 was also 20%-30%higher than those infected by AAV9,implicating better transduction efficiency of AAVc1 in murine muscles.Furthermore,we found that neutralizing antibodies(Nabs)present in rhesus monkey sera against AAVc1 were less than those against AAV9,indicating its less immune response against AAVc1 than AAV9.Altogether,these observations illuminate potential advantages of AAVc1 over wild type AAV serotypes for gene therapy.

关 键 词：基因治疗 腺相关病毒 定向改造 肽展示 肌肉亲和性 

分 类 号：Q782[生物学—分子生物学]