A targeting peptide improves adenovirus-mediated transduction of a glioblastoma cell line

Abstract

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.