HUMAN METABOLIC ENZYMES PRODUCED IN PLANTS

植物中产生的人体代谢酶

• 批准号: 2016854
• 负责人: THOMAS H. TURPEN
• 金额: $ 40.79万
• 依托单位: LARGE SCALE BIOLOGY CORPORATION
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2016854
• 关键词: biological products; drug design /synthesis /production; drug screening /evaluation; enzyme biosynthesis; gene targeting; glucosylceramidase; glycosylation; method development; protein engineering; protein purification; tobacco; tobacco mosaic virus; transfection; transfection /expression vector

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.

相当数量的遗传性代谢性胆固醇储存障碍， 人类 有可能通过补充外源性药物来治疗 产生 内切酶 葡糖脑苷脂酶，来源于人胎盘 组织 或来自中国仓鼠卵巢细胞的重组形式， 使用 有效但昂贵的戈谢病治疗方法。 我们 发现 转基因植物有能力合成 这 具有高比活性人溶酶体酶。 我们开发 一种新型 从烟叶中提取酶的生物处理方法， 提供 至少30倍的酶富集水平， 商业生产。 通过发展全面试点 过程 用于提取和纯化多克量的 葡萄糖脑苷脂酶，我们将建立植物是一个重要的 表示“低”之义 大量复杂重组的成本来源 蛋白 推动现代医学疗法的发展。 我们的目标是 减少 戈谢病患者酶替代疗法的费用; 验证 利用植物作为重组蛋白来源的概念， 临床用于人类;并提供准确的经济生产 模型 来评估未来各种各样的医疗应用。