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.

我们之前从“上下文特异性”噬菌体展示库中选择了肌肉结合肽 12.51 和 12.52，用于引入腺病毒 (Ad) 载体。在这项工作中，这些肽被插入到 Ad5 六邻体蛋白的高变区 (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 将 C2C12 细胞的转导提高了 20 倍。12.51体内增加在小鼠和仓鼠肌肉内注射后，肌肉转导比未修饰的 Ad 高 2 至 7 倍。12.52 没有增加肌肉转导。值得注意的是，与静脉注射后未修饰的 Ad5 相比，将 12.51 插入六邻体减少了 80 倍的肝转导。在基于基因的疫苗接种后，小鼠肌肉转导增加转化为免疫反应增加。这些数据表明，用肽配体修饰 Ads 的六邻体对重新定位和去定位有好处。