MULTIDRUG DELIVERY SYSTEM USING STREPTAVIDIN-TRANSFORMING GROWTH-FACTOR-ALPHA CHIMERIC PROTEIN

Tissue-specific delivery of a variety of molecules has been a valuable technique for biological and medical research. Therefore, we have con structed a recombinant plasmid containing the coding regions for strep tavidin core and mature human transforming growth factor-alpha (TGF-al pha). The recombinant plasmid has been expressed in Escherichia coil t o produce a chimeric protein with both streptavidin and TGF-alpha acti vity. The streptavidin-TGF-alpha chimeric protein (ST-TGF-alpha) could efficiently transfer biotinylated beta-galactosidase into A431 cells via the epidermal growth factor receptor. More than 99% of the cells c ontained the enzyme transferred. Furthermore, ST-TGF-alpha complexed w ith biotinylated-glucose oxidase had a significant cytotoxic effect wh en incubated with A431 cells. These findings suggest that the ST-TGF-a lpha chimeric protein could be used to deliver proteins of interest in to target cells without the need for chemical linkage or genetic const ruction. Essentially, ST-TGF-alpha serves as a high-modular ''molecula r bridge'' for the passage of a wide variety of effector molecules int o target cells.