Retargeted and detargeted adenovirus for gene delivery to the muscle.
Retargeted and detargeted adenovirus for gene delivery to the muscle.
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DOI：
10.1016/j.virol.2017.10.005
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发表时间：
2018-01-15
期刊：
影响因子：
3.7
通讯作者：
Barry MA
中科院分区：
文献类型：
--
作者：
Nguyen TV;Anguiano-Zarate SS;Matchett WE;Barry ME;Barry MA
我们之前从“上下文特异性”噬菌体展示文库中选择肌肉结合肽12.51和12.52导入腺病毒（Ad）载体。在这项工作中，这些肽被插入到Ad5六元蛋白的高变区（HVR） 5环中，每个病毒粒子显示720个肽。与未修饰的Ad5相比，HVR-12.51和12.52使C2C12细胞的转导增加了20倍。12.51在小鼠和仓鼠肌内注射后，体内肌肉转导比未经修饰的Ad增加2至7倍。12.52不增加肌肉转导。值得注意的是，与未经修饰的Ad5相比，在静脉注射后，将12.51插入六邻体可使肝脏转导减少80倍。在基于基因的疫苗接种后，小鼠肌肉转导的增加转化为免疫反应的增加。这些数据表明，用肽配体修饰ad的六邻体具有重靶向和去靶向的优点。
We previously selected muscle binding peptides 12.51 and 12.52 from “context-specific” phage display libraries for introduction into adenovirus (Ad) vectors. In this work, these peptides were inserted into the hypervariable region (HVR) 5 loop of the Ad5 hexon protein to display 720 peptides per virions. HVR-12.51 and 12.52 increased transduction of C2C12 cells up to 20-fold when compared to unmodified Ad5. 12.51 increased in vivo muscle transduction 2 to 7-fold over unmodified Ad after intramuscular injection in mice and hamsters. 12.52 did not increase muscle transduction. Notably, insertion of 12.51 into the hexon reduced liver transduction 80-fold when compared to unmodified Ad5 after intravenous injection. Increased muscle transduction in mice translated into increased immune responses after gene-based vaccination. These data suggest there are merits to retargeting and detargeting benefits to modifying the hexons of Ads with peptide ligands.
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影响因子：
3.7
作者：
Crosby, Catherine M.;Barry, Michael A.
通讯作者：
Barry, Michael A.
影响因子：
12.4
作者：
Liu, F;Nishikawa, M;Huang, L
通讯作者：
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DOI：
10.1073/pnas.93.12.5731
发表时间：
1996-06-11
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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