Grant: Strategic Projects - Group

Whole plants and cultured plant cells are potentially one of the most economical systems for large-scale production of recombinant proteins for industrial and pharmaceutical uses. As the demand for biological drugs increases as predicted, efficient production, in terms of cost and volume, will be critical to meet the rising demand. In the near future, some of the current production systems for generating recombinant proteins for therapeutic purposes will need to be replaced by safer, and more cost-efficient, production systems. Mucopolysaccharidosis I (MPS I) and Gaucher disease are inherited lysosomal storage diseases (LSDs). The former is characterized by a deficiency of an enzyme called alpha-L-iduronidase; in severely affected humans this genetic disease leads to death in early childhood because of profound skeletal, cardiac and neurological disturbances. Purified enzyme is an effective means to restore lysosomal enzyme deficiency. Thus, LSDs, that collectively represent over 50 disorders, are amenable to enzyme replacement therapies (ERT). However, the current methods used to commercially produce recombinant lysosomal enzymes for this purpose, most commonly mammalian cell cultures, are prohibitively costly. Because of this, financial support for ERT on affected Canadians is doubtful. We are using plants as hosts to produce human enzymes toward developing more economical treatments for MPS I and Gaucher disease, and to serve as a general platform for plant production of therapeutic proteins. As well as testing the therapeutic efficacy of our plant-derived enzymes, as a long-term goal, we will establish an in vivo plant-based system for assessing the efficacy of pharmacological chaperones and other small molecules as LSD therapies. This project brings together a unique International team of researchers that have expertise in the genetic basis, pathophysiology, and treatment of human LSDs, protein glycosylation within the context of medicinal chemistry, and recombinant protein production in plants.