Adeno-associated virus serotype rh.10 displays strong muscle tropism following intraperitoneal delivery

被引:22
作者
Ai, Jianzhong [1 ,2 ,3 ]
Li, Jia [2 ]
Gessler, Dominic J. [2 ,3 ]
Su, Qin [2 ]
Wei, Qiang [1 ]
Li, Hong [1 ]
Gao, Guangping [2 ,3 ,4 ]
机构
[1] Sichuan Univ, Inst Urol, West China Hosp, Dept Urol, Chengdu, Sichuan, Peoples R China
[2] Univ Massachusetts, Sch Med, Horae Gene Therapy Ctr, Worcester, MA 01655 USA
[3] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA
[4] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu, Peoples R China
基金
中国博士后科学基金; 美国国家卫生研究院;
关键词
GENE-TRANSFER; VIRAL VECTORS; AAV SEROTYPES; EXPRESSION; LIVER; MICE; TRANSDUCTION; INJECTION;
D O I
10.1038/srep40336
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Recombinant adeno-associated virus (rAAV) is an attractive tool for basic science and translational medicine including gene therapy, due to the versatility in its cell and organ transduction. Previous work indicates that rAAV transduction patterns are highly dependent on route of administration. Based on this relationship, we hypothesized that intraperitoneal (IP) administration of rAAV produces unique patterns of tissue tropism. To test this hypothesis, we investigated the transduction efficiency of 12 rAAV serotypes carrying an enhanced green fluorescent protein (EGFP) reporter gene in a panel of 12 organs after IP injection. Our data suggest that IP administration emphasizes transduction patterns that are different from previously reported intravascular delivery methods. Using this approach, rAAV efficiently transduces the liver, pancreas, skeletal muscle, heart and diaphragm without causing significant histopathological changes. Of note, rAAVrh.10 showed excellent muscle transduction following IP administration, highlighting its potential as a new muscle-targeting vector.
引用
收藏
页数:6
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