The goal of this SBIR proposal is to develop transgenic tobacco as a cost effective bioproduction system for the human alpha-L-iduronidase (E.C. 3.2.1.76). Iduronidase (IDUA) enzyme activity is deficient in the mucopolysaccharidosis I class (Hurler, Hurler-Scheie and Scheie syndromes) of lysosomal storage disorders. Enzyme replacement using exogenous IDUA has been shown to be effective in cell culture and animal disease models but the limited supply of pure IDUA seriously hampers research needed to develop this approach into an effective therapy. Transgenic tobacco has the potential to express human IDUA in large amounts sufficient to produce a cost-effective source of protein for research and therapeutic needs.
The aim of Phase I is to demonstrate the ability of tobacco plant cells to express the human IDUA gene. Specific objectives are 1) to engineer human IDUA cDNA's into appropriate plant transformation/expression vectors, and 2) to introduce the IDUA gene into tobacco and monitor transgene expression and IDUA production. Success in these objectives would support Phase II research aimed at optimizing production of bioactive human IDUA in transgenic tobacco. New technology developed as part of this project Could, additionally, be applied to plant bioproduction of other pharmaceuticals.
