We have developed a system to deliver DNA to mammalian cells utilizing a protein with specific receptor and DNA binding properties. The fusion protein was constructed with transforming growth factor a (TGFa) at the N-terminus and human telomeric repeat binding factor (hTRF) at the C-terminus (TGFa/TRF), expressed in E.coli, refolded from inclusion bodies and purified through ion exchange columns and a telomeric DNA (T2AG3 repeats)- specific affinity column. Binding to telomeric DNA was evident by mobility shift assay. TGFa binding activity to the epidermal growth factor (EGF) receptor was confirmed by competition studies whereby TGFa/TRF displaced 125I-EGF from EGF receptors. Plasmid DNA containing T2AG3 repeats and the E. coli Lac Z beta- gal) reporter gene was bound to TGFa/TRF and the complexes were condensed by poly-L-lysine (pL), and added to cells.beta-gal expression was observed in EGF expressing cells above the background of pL alone and this increase in beta-gal expression was blocked in the presence of excess EGF protein. We have attempted to confirm the specificity and improved the efficiency of transfection usin this type of fusion protein by incorporating translocation domains to enhance intracellular trafficking of DNA to the nucleus. Since results do not indicate significant improvement after the inclusion of translocating domains and suggest that DNA binding to the fusion protein alters the ability of the protein to bind to the cell surface receptor, we have shifter our focus to a different but closely related DNA binding protein (TRF2). TRF2 has a higher binding affinity than TRF1 and may have a different binding conformation. Similar constructs will be made with TRF2 and tested for their ability to bind to telomeric DNA and transfer that DNA into mammalian cells