HUMAN METABOLIC ENZYMES PRODUCED IN PLANTS

植物中产生的人体代谢酶

• 批准号: 2668318
• 负责人: THOMAS H. TURPEN
• 金额: $ 26.96万
• 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/2668318
• 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.

相当多的遗传性代谢储存障碍 人类 可以通过补充外源性药物来治疗 产生的 酶。 葡萄糖脑苷脂酶，源自人胎盘 组织 或来自中国仓鼠卵巢细胞的重组形式，目前 用过的 戈谢病的有效但昂贵的治疗方法。 我们 发现了 转基因植物有能力合成 这 具有高比活性的人溶酶体酶。 我们开发了 一本小说 生物加工方法从烟叶中提取酶， 提供 至少将酶富集 30 倍，达到能够 商业化生产。 通过开展全面试点 过程 用于提取和纯化数克量的 葡萄糖脑苷脂酶，我们将确定植物是重要的 低的- 大量复杂重组的成本来源 蛋白质 推进现代医学治疗所必需的。 我们的目标是 减少 戈谢病患者酶替代疗法的费用； 证实 使用植物作为重组蛋白来源的概念 人类临床应用；并提供准确的经济生产 模型 评估各种未来的医疗应用。