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Cancer Res. 2010 Dec 1;70(23):9549-53. Epub 2010 Jul 29.

Adenovirus targeting to prostate-specific membrane antigen through virus-displayed, semirandom peptide library screening.

Wu P, Kudrolli TA, Chowdhury WH, Liu MM, Rodriguez R, Lupold SE.

Source

The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

Abstract

The convergence of phage-displayed peptide libraries and recombinant viral vectors launched a promising new direction in targeted viral gene therapeutics, but the translation of targeting peptides to functional cancer therapeutic agents has been challenging. Here, we report progress in developing a successful strategy to optimize targeted viral infection through adenovirus-displayed, semirandom peptide libraries. A phage-derived peptide targeting the prostate-specific membrane antigen (PSMA) was genetically incorporated into the adenoviral capsid Fiber protein and flanked by random peptide cassettes. The resulting adenovirus library was biopanned against PSMA-expressing cells and tumors to identify a PSMA-retargeted adenovirus. While the initial peptide alone could not target viral infection, the selected virus preferentially infects PSMA-expressing cells through the targeting peptide and infects LNCaP tumors after intravenous injection. Our results indicate that virus-displayed, semirandom peptide libraries can be used to optimize targeting infection. This approach represents a novel principle for developing targeted agents in a variety of disease models.

PMID:: 20670952; [PubMed - indexed for MEDLINE]
PMCID:: PMC2995819

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