Engineering epidermal growth factor for enhanced mitogenic potency

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Abstract
Successful use of growth factois in therapeutic and bioprocessig application requires overcoming two attenuation mechanisms: growth factor depletion and receptor down-regulation. current ameliorative strategies use physiologically inappropriate high growth-factor concentrations, along with periodic media refeeding in vitro and reinjection or controlled-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 migogenic stimulus of fibroblasts than natural EGF or transforming growth factor alpha because of its altered trafficking properties.