Gene transfer to mammalian cells using genetically targeted filamentous bacteriophage

We have genetically modified filamentous bacteriophage to deliver genes to mammalian cells. In previous studies we showed that noncovalently attached fibroblast growth factor (FGF2) can target bacteriophage to COS-1 cells, re sulting in receptor-mediated transduction with a reporter gene, Thus, bacte riophage, which normally lack tropism for mammalian cells, can be adapted f or mammalian cell gene transfer. To determine the potential of using phage- mediated gene transfer as a novel display phage screening strategy, we tran sfected COS-1 cells with phage that were engineered to display FGF2 on thei r surface coat as a fusion to the minor coat protein, pIII, Immunoblot and ELISA analysis confirmed the presence of FGF2 on the phage coat. Significan t transduction was obtained in COS-1 cells with the targeted FGF2-phage com pared with the nontargeted parent phage, Specificity was demonstrated by su ccessful inhibition of transduction in the presence of excess free FGF2, Ha ving demonstrated mammalian cell transduction by phage displaying a known g ene targeting ligand, it is now feasible to apply phage-mediated transducti on as a screen for discovering novel ligands.