PRODUCTION AND CHARACTERIZATION OF FUSION PROTEINS CONTAINING TRANSFERRIN AND NERVE GROWTH-FACTOR

To explore the ability to use genetic fusions of transferrin as a carr ier for brain targeting and delivery a series of fusion proteins conta ining both human nerve growth factor (NGF) and human transferrin was p roduced in mammalian cells. A protein in which the hinge region from h uman IgG(3) joined the carboxyl terminus of NGF and the amino terminus of transferrin formed a covalent homodimer, bound human transferrin r eceptor, and retained full NGF in PC12 cells. In contrast, proteins in which polypeptide dimerization was not induced or in which NGF was fu sed through its amino terminus had greatly reduced NGF activity. The a bility to maintain both biologically active NGF and transferrin as par t of a fusion protein may offer a novel way to deliver NGF and other n eurotrophic factors to the central nervous system.