Adenoviral Gene Therapy Vectors Targeted to Prostate Cancer
Final rept. 1 Jun 2001-31 May 2004
SCRIPPS RESEARCH INST LA JOLLA CA
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The goal of this project was the development of adenoviruses conditionally-replicating adenoviruses, CRA that will more selectively infect, replicate in, and kill prostate tumor cells. There were three Aims Tasks 1 evaluate existing Ad serotypes for their possible utility, 2 use phage display technology to isolate prostate tumor-binding peptides, and 3 to combine the best targeting strategy identified with prostate tumor-selective Ad replication. We made substantial progress in Aims 1 and 2, and identified two promising native fiber proteins for further use. Our work with the synthetic prostate tumor-binding peptides was in the end less successful. While a number of peptides that bound the cells were identified, none of these proved to be of utility in the context of the adenoviral fiber protein. Aim 3 was designed to use the fibers identified in the first two Aims in construction of a replicating adenovirus driven by the osteocalcin promoter. We isolated this promoter and constructed plasmids in which the viral E1a a gene or beta-galactosidase was driven by osteocalcin, for use in virus construction. In contrast to numerous previous reports, we did not see significant promoter activity following transfection of cells. Replicating viruses with this promoter were not constructed.
- Medicine and Medical Research