Phage display of adenoviral HI loop for "context-specific" ligand selection

Abstract

Adenoviruses are used as delivery vectors in gene therapy mainly due to their ability to efficiently infect dividing and non-dividing cells. However, their success is hindered due to its tropism for non-targeted cell types. Adenoviruses can be genetically retargeted by ligand addition to confer specificity. Phage-presenting random peptide libraries have been used to select potential ligands. This approach does not require knowledge of the cell biology. However, selected peptides engineered into the adenovirus can reduce viral capsid function, and the adenovirus can impair targeting ability of the selected peptide. Our research focuses on the development of "context-specific" random libraries for ligand selection. By introducing a viral context, we hope to select a peptide that can be introduced into the virus without affecting function. In this paper, we report the phage display of biotin acceptor peptide within the adenoviral HI loop (denoted HI-BAP). HI-BAP is expressed and enzymatically biotinylated on the pIII minor coat protein of filamentous phage. This approach can improve targeting of viral vectors.