A targeting peptide improves adenovirus-mediated transduction of a glioblastoma cell line.
A targeting peptide improves adenovirus-mediated transduction of a glioblastoma cell line.
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DOI：
10.3892/or.2014.3065
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发表时间：
2014-05
期刊：
影响因子：
4.2
通讯作者：
Dongyang Wang;Wenbo Li;Hang Zhang;Q. Mao;Haibin Xia
中科院分区：
文献类型：
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作者：
Dongyang Wang;Wenbo Li;Hang Zhang;Q. Mao;Haibin Xia
由于在多种肿瘤类型上缺乏腺病毒受体的天然表达，阻碍了腺病毒在肿瘤基因治疗中的应用进展。因此，需要策略将腺病毒载体重新靶向到非天然细胞表面受体。在本研究中，通过噬菌体展示肽库的直接生物筛选，鉴定了一种能够选择性靶向人胶质母细胞瘤细胞系A172的新肽SWDIAWPPLKVP。在A172中显示SWDIAWPPLKVP肽的噬菌体的结合活性比对照噬菌体高10倍以上。然后我们将选择的肽SWDIAWPPLKVP插入腺病毒六邻体蛋白中，观察到修饰后的Ad5在A172细胞中的感染性比在对照细胞系中的感染性强。这些发现表明，通过噬菌体展示获得的肽在插入Ad六邻体时可以介导细胞特异性Ad重靶向，这提示了一种靶向腺病毒感染特异性癌细胞的方法。
The progress of the application of adenovirus in cancer gene therapy is hindered by the lack of expression of native adenovirus receptor on a variety of cancer types. Hence, strategies are needed to retarget the adenoviral vector to non-native cellular surface receptors. In the present study, a new peptide SWDIAWPPLKVP, capable of selectively targeting a human glioblastoma cell line A172, was identified by direct biopanning of phage-display peptide libraries. The binding activity of the phage displaying SWDIAWPPLKVP peptide in A172 was more than 10-fold higher than that of the control phage. We then inserted the selected peptide SWDIAWPPLKVP into adenoviral hexon protein, and observed that the modified Ad5 had increased infectivity in A172 cells, compared with that in control cell lines. These findings demonstrated that a peptide acquired through phage display can mediate cell-specific Ad retargeting when inserted into Ad hexon, suggesting an approach for targeting adenoviral infection to specific cancer cells.