The engineering fo viral cell ligands is a very new strategy to direct cell binding and entry of visuses with altered cell tropism, and potentially of DNA-protein complexes, structural proteins, peptides, oligonucleotides, enzymes and toxins, in specific cell lines or tissues. Recent data from our group demonstrate the potential of short viral stretches carrying the RGD motif, to direct binding and internalization of macromolecular complexes enymatically actives in cells expressing the target integrin. We propose the engineering of such peptides and their modification by molecular evolution to improve and modulate their specificity, the study of the intracellular fate of these chimeric proteins, and their stability and half-lifes inside the cell. We also suggest to fuse these peptides to DNA binding domains and eventually cekk toxins or enzymes to explore the potential of this sistem for the design of new antitumoral and antiviral drugs and also in antisense therapy. On the other hand, we propose the molecular cloning and expression of genes encoding chimeric antibodies and the analysis of the multifunctional products as ligands and immunoreactives. We will evaluate the usefulness of \i E.coli\i0 as cell factory the synthesis of such multifunctional recombinant proteins, by the detailed analysis of the bottle necks limiting their production.
|Effective start/end date||1/09/98 → 1/09/01|