Ruben J. Boado, Jeff Zhiqiang Lu, Eric K.-W. Hui, Rachita K. Sumbria and William M. Pardridge Pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptor Biotechnology and Bioengineering 110
Targeted-delivery of the lysosomal enzyme, arylsulfatase A (ASA), across the blood-brain barrier (BBB) for treatment of the brain in metachromatic leukodystrophy is possible following the re-engineering of the enzyme as an IgG-enzyme fusion protein. The IgG domain of the fusion protein is a genetically engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The monoclonal antibody acts as a molecular Trojan horse to ferry the enzyme into brain via transport on the endogenous BBB insulin receptor.
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