Drugs through Bugs: Expression of Naglu-­‐PTD4 in Spodoptera frugiperda

Abstract

Mucopolysaccharidosis IIIB (MPS IIIB) is a rare metabolic disorder that is caused by a deficiency in the lysosomal hydrolase α-N-acetylglucosaminidase (Naglu). The deficient activity of this enzyme results in the cytotoxic accumulation of heparan sulfate in the lysosome. Patients with this disorder experience progressive central nervous system degeneration and a significantly shortened life span. Presently, enzyme replacement therapy is an ineffective treatment for MPS IIIB due to the inability of exogenous Naglu to permeate the blood-brain barrier. This project uses the Sf9 insect cell system to express human recombinant Naglu fused to a synthetic protein transduction domain with the intent to facilitate the delivery of Naglu across the blood-brain barrier. The overall goal of this project is to establish a large-scale, economical system for the production of human recombinant Naglu that has the potential to be successfully used for enzyme replacement therapy to treat MPS IIIB.