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GDNF fusion protein for targeted-drug delivery across the human blood–brain barrier by Ruben J. Boado; Yun Zhang; Yufeng Zhang; Yuntao Wang; William M. Pardridge is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is GDNF fusion protein for targeted-drug delivery across the human blood–brain barrier about?

## Abstract Glial‐derived neurotrophic factor (GDNF) is a neurotrophin that could be developed as a neurotherapeutic for Parkinson's disease, stroke, and motor neuron disease. However, GDNF does not cross the blood–brain barrier (BBB). Human GDNF was re‐engineered by fusion of the mature GDNF protein to the carboxyl terminus of the chimeric monoclonal antibody (MAb) to the human insulin receptor (HIR). The HIRMAb‐GDNF fusion protein is bi‐functional, and both binds the HIR, to trigger receptor‐mediated transport across the BBB, and binds the GDNF receptor (GFR)‐α1, to activate GDNF neuroprotection pathways behind the BBB. COS cells were dual transfected with the heavy chain (HC) and light chain fusion protein expression plasmids, and the HC of the fusion protein was immunoreactive with antibodies to both human IgG and GDNF. The HIRMAb‐GDNF fusion protein bound with high affinity to the extracellular domain of both the HIR, ED~50~ = 0.87 ± 0.13 nM, and the GFRα1, ED~50~ = 1.68 ± 0.17 nM. The HIRMAb‐GDNF fusion protein activated luciferase gene expression in human neural SK‐N‐MC cells dual transfected with the c‐ret kinase and a luciferase reporter gene under the influence of the rat

Who reads GDNF fusion protein for targeted-drug delivery across the human blood–brain barrier?

Author

Ruben J. Boado; Yun Zhang; Yufeng Zhang; Yuntao Wang; William M. Pardridge

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); Wiley - V C H Verlag GmbbH & Co.; Wiley (ISSN 0006-3592)

Published

2007

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)