Recent studies in animal models demonstrate that an endogenous human intestinal mucin fragment, termed MUC17, augments intestinal cell restitution and enhances healing of experimental colitis, potentially opening a new door to effective treatment of ulcerative colitis. However, expression of MUC17 in E. coli, yeast, and insect cells has met great challenges due to low expression, improper folding or insolubility. Ventria scientists have developed a highly efficient protein expression system in rice grain and have used the system to produce several proteins which are now in the marketplace. In the present proposal, we would like to test the feasibility of employing the proprietary Ventria rice expression system to produce MUC17 at high levels. Furthermore, we will purify MUC17 from rice grain and test its biological function via in vitro cell culture studies. We hypothesize that MUC17, derived from rice grain, will promote cell migration and inhibit apoptosis, important functions in epithelial cell restitution of the colon. Successfully expressing functional MUC17 in rice grain at high levels will greatly enhance the research and development effort of this project and provide a path to commercialization of this novel protein for patients suffering from ulcerative colitis.
Public Health Relevance Statement: Public Health Relevance: Ulcerative colitis is a chronic debilitating disease which is prevalent primarily in the Western world. Currently therapies rely on anti-inflammatory strategies (mesalamine and steroids) which are palliative at best, or expensive TNF antibodies which have associated toxicities. In the present application, we propose to use Ventria's world- leading protein expression system to produce high levels of human MUC17 fragment, an endogenous agent which restores the epithelial lining of the colon, thereby enabling commercialization of this novel protein in the treatment of ulcerative colitis.
NIH Spending Category: Autoimmune Disease; Biotechnology; Digestive Diseases; Inflammatory Bowel Disease
Project Terms: Animal Model; Anti-inflammatory; Anti-Inflammatory Agents; Antibodies; Apoptosis; base; Biological Assay; Biological Process; Blood; Cell Culture Techniques; cell motility; Cells; Cereals; Chinese Hamster Ovary Cell; Chronic; Colitis; Colon; commercialization; cost; Crohn's disease; Diarrhea; Diffuse; Disease; Disease remission; Economic Burden; effective therapy; Effectiveness; enema administration; Epithelial; Epithelial Cells; Escherichia coli; Evaluation; experience; Family; Feasibility Studies; Funding; Healed; healing; Human; In Vitro; in vivo; Inflammatory Bowel Diseases; Insecta; Intestines; Lead; meetings; Mesalamine; Morbidity - disease rate; Mucins; novel; palliative; Patients; Phase; Plants; preclinical study; Preparation; prevent; Production; protein expression; protein misfolding; Proteins; public health relevance; Quality of life; Recombinant Proteins; Recombinants; Rectal Administration; Request for Proposals; research and development; research clinical testing; response; Rice; safety study; scale up; Scientist; Seeds; Small Business Innovation Research Grant; Societies; Steroids; Symptoms; System; Technology; Testing; TNF gene; Toxic effect; Toxicology; Transgenic Organisms; Transgenic Plants; Ulcer; Ulcerative Colitis; United States; Western World; Yeasts
