Production and characterization of fusion proteins containing transferrin and nerve growth factor.
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 PC12 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.
Park
E
E
Alkermes, Inc., Cambridge, MA 02139, USA.
Starzyk
R M
RM
McGrath
J P
JP
Lee
T
T
George
J
J
Schutz
A J
AJ
Lynch
P
P
Putney
S D
SD
D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011990:Receptors, Transferrin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000494:pharmacology*; D014168:Transferrin / Q000008:administration & dosage*
D004337:Drug Carriers; D009414:Nerve Growth Factors; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D014168:Transferrin