ENGINEERING EPIDERMAL GROWTH-FACTOR FOR ENHANCED MITOGENIC POTENCY

Successful use of growth factors in therapeutic and bioprocessing appl ications requires overcoming two attenuation mechanisms: growth factor depletion and receptor down-regulation. Current ameliorative strategi es use physiologically inappropriate high growth-factor concentrations , along with periodic media refeeding in vitro and reinjection or cont rolled-release devices in vivo. We demonstrate a new approach derived from understanding how these attenuation mechanisms arise from ligand/ receptor trafficking processes. Specifically, a recombinant epidermal growth factor (EGF) mutant with reduced receptor binding affinity is a more potent mitogenic stimulus for fibroblasts than natural EGF or tr ansforming growth factor alpha because of its altered trafficking prop erties.