Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer.
Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer.
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DOI：
10.1038/gt.2014.56
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发表时间：
2014-09
期刊：
影响因子：
5.1
通讯作者：
Marasco WA
中科院分区：
文献类型：
--
作者：
Abdel-Motal UM;Harbison C;Han T;Pudney J;Anderson DJ;Zhu Q;Westmoreland S;Marasco WA
Topical microbicides are a leading strategy for prevention of HIV mucosal infection to women, however, numerous pharmacokinetic limitations associated with coitally-related dosing strategy have contributed to their limited success. Here we test the hypothesis that adeno-associated virus (AAV) mediated delivery of the b12 human anti-HIV-1 gp120 minibody gene to the lower genital tract of female rhesus macaques (Rh) can provide prolonged expression of b12 minibodies in the cervical-vaginal secretions. Gene transfer studies demonstrated that, of various GFP-expressing AAV serotypes, AAV-6 most efficiently transduced freshly immortalized and primary genital epithelial cells (PGECs) of female Rh in vitro. In addition, AAV-6-b12 minibody transduction of Rh PGECs led to inhibition of SHIV162p4 transmigration and virus infectivity in vitro. AAV-6-GFP could also successfully transduce vaginal epithelial cells of Rh when applied intra-vaginally, including p63+ epithelial stem cells. Moreover, intra-vaginal application of AAV-6-b12 to female Rh resulted in prolonged minibody detection in their vaginal secretions throughout the 79 day study period. These data provide proof-of-principle that AAV-6-mediated delivery of anti-HIV broadly neutralizing antibody (BnAb) genes to the lower genital tract of female Rh results in persistent minibody detection for several months. This strategy offers promise that an anti-HIV-1 genetic microbicide strategy may be possible in which topical application of AAV vector, with periodic reapplication as needed, may provide sustained local BnAb expression and protection.
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影响因子：
32.4
作者：
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通讯作者：
McElrath, M. Juliana
使用单个 AAV 载体转导和食品和药物管理局批准的药物增强的锌指核酸酶介导的基因校正。
影响因子：
5.1
作者：
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通讯作者：
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DOI：
10.1111/j.1600-0897.2007.00561.x
发表时间：
2008-01-01
影响因子：
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作者：
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影响因子：
64.8
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影响因子：
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