Gene delivery GAD500 autoantigen by AAV serotype 1 prevented diabetes in NOD mice:: Transduction efficiency do not play important roles

被引：12

作者：

Han, Gencheng ^{[1
]}

Wang, Renxi ^{[1
]}

Chen, Guojiang ^{[1
]}

Wang, Ranan ^{[1
]}

Xu, Ruonan ^{[1
]}

Feng, Jiannan ^{[1
]}

Yu, Ming ^{[1
]}

Wu, Xiaobing ^{[2
]}

Qian, Jiahua ^{[3
]}

Shen, Beifen ^{[1
]}

Li, Yan ^{[1
]}

机构：

[1] Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China

[2] Natl Key Lab Mol Virol & Genet Engn, Beijing, Peoples R China

[3] Natl Canc Inst, Vaccine Branch, Bethesda, MD 20889 USA

来源：

IMMUNOLOGY LETTERS | 2008年 / 115卷 / 02期

基金：

中国国家自然科学基金;

关键词：

autoimmune diabetes; gene therapy; AAV-1; AAV-2;

D O I：

10.1016/j.imlet.2007.10.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We previously found that adeno-associated viral vector serotype 2 (AAV-2) muscle gene delivery of GAD(500-585) autoantigen efficiently prevented autoimmune diabetes in NOD mice. Recent reports suggest that AAV vectors based on serotype 1 (AAV-1) transduce murine skeletal muscle much more efficiently than AAV-2, with reported increases in expression ranging from 2 to 1000-fold. To determine whether this increased efficacy of AAV-1 could result in increased therapeutic effects in mice, we constructed rAAV(1)/GAD(500-585) vectors and compared their effects in preventing autoimmune diabetes in NOD mice with those of rAAV(2)/GAD(500-585) after muscle injection. rAAV(1)/GAD(500-585) gene therapy prevented diabetes in NOD mice. However, although much higher level of GAD500-585 expression was found in mice using AAV-1 as gene delivery vector than those using AAV-2, no increased efficiency of AAV-1 vectors were found in their capability to prevent autoimmune diabetes, as higher titers of rAAV1/GAD(500-585) virus (3 x 10(11) v.g./mouse) were needed to obtain therapeutic effects in NOD mice, a titer not different from that of AAV2. Protection resulted from rAAV(1)/GAD(500-585) gene therapy were marked by enhanced Th2 immune response and up-regulated CD4(+)Foxp(3+)T regulatory cells, which might actively suppress effector T cells in NOD mice. As here we found that the therapeutic effects of AAV1 were not positively correlated to it's transduction efficiency, our data suggested that the safety and other factors besides efficiency should be considered when use different AAV serotype to treat autoimmune disease. (C) 2007 Elsevier B.V. All rights reserved.

引用

页码：110 / 116

页数：7