Effective repeat administration with adenovirus vectors to the muscle

被引:63
作者
Chen, P [1 ]
Kovesdi, I [1 ]
Bruder, TJ [1 ]
机构
[1] GenVec Inc, Gaithersburg, MD 20878 USA
关键词
adenovirus; gene therapy; humoral immunity; muscle; antibody; neutralization;
D O I
10.1038/sj.gt.3301137
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Effective repeat administration of adenovirus vectors following intranasal or intravenous delivery is hindered by a strong neutralizing antibody response to the vector Intramuscular administration of adenovirus vectors elicited a neutralizing antibody response that peaked between 14 and 21 days after infection. However, effective repeat intramuscular administration of adenovirus vectors was not hindered by the presence of neutralizing antibodies in the serum. Surprisingly, beta-galactosidase expression in the skeletal muscle of immunized mice was equivalent to that observed in control mice. As expected, these serum neutralizing antibodies effectively blocked repeat administration of adenovirus vectors when delivered via the intravenous route. These results were observed in both C57BL/6 and Balb/c mice and thus do not appear to be strain specific. Successful repeat administration of adenovirus vectors to skeletal muscle has significant implications for the use of adenovirus vectors clinically and for increasing the safety and efficacy of adenovirus vector gene delivery.
引用
收藏
页码:587 / 595
页数:9
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