Human Iduronidase (Hurler Syndrome) Expression in Plants

This research will develop transgenic tobacco as a cost effective bioproduction system for thehuman alpha-L-iduronidase (E.C. 3.2.1.76). Iduronidase (IDUA) enzyme activity is deficient in themucopolysaccharidosis I class (Hurler, Hurler-Scheie and Scheie syndromes) of lysosomal storagedisorders. Enzyme replacement using exogenous IDUA has been shown to be effective in cell cultureand animal disease models but the limited supply of pure IDUA seriously hampers research needed todevelop this approach into an effective therapy. Transgenic tobacco has the potential to express humanIDUA in large amounts sufficient to produce a cost-effective source of protein for research andtherapeutic needs. Phase I will demonstrate the ability of tobacco plant cells to express the human IDUAgene. Specific objectives are 1) to engineer human IDUA cDNA's into appropriate plant transforma-tion/expression vectors, and 2) to introduce the IDUA gene into tobacco and monitor transgeneexpression and IDUA production. Success in these objectives would support Phase II research aimed atoptimizing production of bioactive human IDUA in transgenic tobacco. New technology developed as partof this project Could, additionally, be applied to plant bioproduction of other pharmaceuticals.