Production and Characterization of Fusion Proteins Containing Transferrin and Nerve Growth Factor

E. Park Alkermes, Inc., 64 Sidney Street, Cambridge, MA, 02139, USA; Massachusetts General Hospital, Boston, MA, 02114, USA

R. M. Starzyk Alkermes, Inc., 64 Sidney Street, Cambridge, MA, 02139, USA; Genetics Institute, Cambridge, MA, 02140, USA

J. P. McGrath Alkermes, Inc., 64 Sidney Street, Cambridge, MA, 02139, USA

T. Lee Alkermes, Inc., 64 Sidney Street, Cambridge, MA, 02139, USA; Department of Biology, MIT, Cambridge, MA, 02139, USA

J. George Alkermes, Inc., 64 Sidney Street, Cambridge, MA, 02139, USA; BASF Bioresearch Corporation, Worcester, MA, 01605, USA

A. J. Schutz Alkermes, Inc., 64 Sidney Street, Cambridge, MA, 02139, USA; Genzyme Corporation, Cambridge, MA, 02139, USA

P. Lynch Alkermes, Inc., 64 Sidney Street, Cambridge, MA, 02139, USA; PerSeptive Biosystems, Framingham, MA, 01701, USA

S. D. Putney Alkermes, Inc., 64 Sidney Street, Cambridge, MA, 02139, USACorrespondence[email protected]

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Abstract

To explore the ability to use genetic fusions of transferrin as a carrier for brain targeting and delivery, a series of fusion proteins containing both human nerve growth factor (NGF) and human transferrin was produced in mammalian cells. A protein in which the hinge region from human IgG₃ joined the carboxyl terminus of NGF and the amino terminus of transferrin formed a covalent homodimer, bound human transferrin receptor, and retained full NGF in PC 12 cells. In contrast, proteins in which polypeptide dimerization was not induced or in which NGF was fused through its amino terminus had greatly reduced NGF activity. The ability to maintain both biologically active NGF and transferrin as part of a fusion protein may offer a novel way to deliver NGF and other neurotrophic factors to the central nervous system.

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Production and Characterization of Fusion Proteins Containing Transferrin and Nerve Growth Factor

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Production and Characterization of Fusion Proteins Containing Transferrin and Nerve Growth Factor

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