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Cancer Res. 2010 Dec 1;70(23):9549-53. doi: 10.1158/0008-5472.CAN-10-1760. Epub 2010 Jul 29.

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

Author information

1
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
PMCID:
PMC2995819
DOI:
10.1158/0008-5472.CAN-10-1760
[Indexed for MEDLINE]
Free PMC Article

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