Production of human MUC17 (CRD1-L-CRD2) recombinant protein in rice for the treat

在水稻中生产人 MUC17 (CRD1-L-CRD2) 重组蛋白用于治疗

• 批准号: 8451917
• 负责人: NING HUANG
• 金额: $ 23.73万
• 依托单位: VENTRIA BIOSCIENCE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8451917
• 关键词: Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Apoptosis; Biological Assay; Biological Process; Blood; Cell Culture Techniques; Cells; Cereals; Chinese Hamster Ovary Cell; Chronic; Colitis; Colon; Crohn' s disease; Diarrhea; Diffuse; Disease; Disease remission; Economic Burden; Effectiveness; Epithelial; Epithelial Cells; Escherichia coli; Evaluation; Family; Feasibility Studies; Funding; Healed; Human; In Vitro; Inflammatory Bowel Diseases; Insecta; Intestines; Lead; Mesalamine; Morbidity - disease rate; Mucins; Patients; Phase; Plants; Preparation; Production; Proteins; Quality of life; Recombinant Proteins; Recombinants; Rectal Administration; Request for Proposals; Rice; Scientist; Seeds; Small Business Innovation Research Grant; Societies; Steroids; Symptoms; System; TNF gene; Technology; Testing; Toxic effect; Toxicology; Transgenic Organisms; Transgenic Plants; Ulcer; Ulcerative Colitis; United States; Western World; Yeasts; base; cell motility; commercialization; cost; effective therapy; enema administration; experience; healing; in vivo; meetings; novel; palliative; preclinical study; prevent; protein expression; protein misfolding; public health relevance; research and development; research clinical testing; response; safety study; scale up

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：最近在动物模型中的研究表明，一种内源性的人肠粘蛋白片段MUC17可以增强肠细胞的恢复并促进实验性结肠炎的愈合，可能为溃疡性结肠炎的有效治疗打开了一扇新的大门。然而，MUC17在大肠杆菌、酵母和昆虫细胞中的表达由于低表达、折叠不当或不溶性而遇到了很大的挑战。Ventria的科学家们已经开发出了一种高效的大米蛋白质表达系统，并利用该系统生产了几种现已上市的蛋白质。在目前的提案中，我们想测试使用专有的Ventria水稻表达系统产生高水平MUC17的可行性。此外，我们将从水稻中纯化MUC17，并通过体外细胞培养研究来测试其生物学功能。我们推测来自稻米的MUC17能够促进细胞迁移和抑制细胞凋亡，在结肠上皮细胞修复中发挥重要作用。成功在水稻中高水平表达功能性MUC17将大大加强该项目的研究和开发工作，并为溃疡性结肠炎患者提供这种新型蛋白的商业化途径。