A considerable number of hereditary metabolic storage disorders of humans are potentially treatable by supplementation with exogenously produced enzymes. Glucocerebrosidase, either derived from human placental tissue or a recombinant form from Chinese hamster ovary cell, is presently used in an effective but costly treatment of Gaucher disease. We discovered that genetically modified plants have the capacity to synthesize this human lysosomal enzyme with high specific activity. We developed a novel bioprocessing method to extract the enzyme from tobacco leaves, providing at least a 30-fold enrichment for enzyme to levels that will enable commercial production. Through development of a full-scale pilot process for the extraction and purification of multigram quantities of glucocerebrosidase, we will establish that plants are an important low- cost source for the large quantities of complex recombinant proteins required to advance modern medical therapies. Our goals are to reduce the costs of enzyme replacement therapy for Gaucher patients; validate the concept of using plants as a source of recombinant proteins for clinical use in humans; and provide an accurate economic production model to evaluate a wide variety of future medical applications.
