Selective DNA Delivery to Breast Cancer Cells
Annual rept. 1 Jun 2000-31 May 2001
ROCHESTER UNIV NY
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We hypothesize that one can use specific protein or peptide sequences to direct linked DNA molecules to breast cancer cells this hypothesis is being experimentally tested. During the period covered by this progress report, we have shown that we have conducted proof-of-concept studies to show that we can selectively target adenovirus vectors to a defined cell type of interest, using peptides derived by screening of phage display libraries. We are now proceeding with experiments aimed at targeting adenovirus vectors to breast cancer cells. We have generated molecules capable of binding with high affinity to the alpha v beta 3 integrin alpha v beta 3 is an endocytosing receptor that is expressed on many breast cancers. These molecules were derived from a randomized library of mutants of the tenth domain from human fibronectin FN3, displayed on the surface of M13 phage. The alpha v beta 3-binding FN3 mutants are small proteins with great stability and much stronger binding affinity than short peptides. We are now examining whether these FN3 molecules can mediate DNA transfer into alpha v beta 3-positive cells, including breast cancer cells. The findings obtained to date have provided us with important reagents for further studies, including analyses of gene transfer into breast cancer cells, both in vitro and in vivo.
- Medicine and Medical Research