Enhancement of the glycosylation machinery of the hen bioreactor

母鸡生物反应器糖基化机制的增强

• 批准号: 7801263
• 负责人: MARK C. LEAVITT
• 金额: $ 37.76万
• 依托单位: SYNAGEVA BIOPHARMA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7801263
• 关键词: Animal Model; Animals; Biological Availability; Biological Products; Bioreactors; Biotechnology; Cells; Characteristics; Chickens; Chinese Hamster; Chinese Hamster Ovary Cell; Clinical Trials; Code; Data; Deposition; Disease; Dose; Egg White; Egg White Proteins; Elements; Embryo; Engineering; Enzymes; Erythrocytes; Erythropoietin; Future; Galactose; Generations; Genomics; Goals; Half-Life; Human; Industry; Licensing; Link; Maintenance; Mammalian Oviducts; Marketing; Oligosaccharides; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plants; Polysaccharides; Post-Translational Protein Processing; Preparation; Production; Proteins; Resources; Safety; Sialic Acids; Structure; System; Technology; Therapeutic; Transferase; Transgenes; Transgenic Organisms; arm; base; commercialization; cost; egg; glycosylation; meetings; novel; novel therapeutics; public health relevance; sugar

DESCRIPTION (provided by applicant): The impact of protein-based pharmaceuticals in the treatment of disease continues to surge, driven by discoveries in genomics and successful implementation by the biotechnology industry. The production of proteins remains a challenge because of the increasing demand and need for large doses. Many proteins require post-translational modifications that are only efficiently synthesized by vertebrate cells. Vertebrate cells, such as the industry standard Chinese Hamster Cells (CHO), can be difficult to grow under GMP conditions and require immense resources to propagate at the scale needed to meet market demands. Animal and plant based bioreactors systems are an attractive alternative to CHO due to low maintenance costs and ease of scalability. However, the post-translational modification of biopharmaceuticals, in particular glycosylation, is executed differently in animals and plants as compared to CHO cells. The hen, because of its prolific egg laying and protein production abilities, has been pursued as a biopharmaceutical bioreactor. The sugar molecules attached to certain proteins produced in eggs of transgenic hens have been found to share the same basic structure with CHO and human proteins. However there are some structural elements that are lacking in the egg white-derived sugars that could be important for bioactivity and bioavailability in human patients. The goal of this project is to genetically engineer hens to impart wholly-human like sugar structures upon egg white-derived biopharmaceuticals. PUBLIC HEALTH RELEVANCE: The proposed project, creation of transgenic hens that produce human biopharmaceuticals with human-like characteristics, will be a major step in the maturation of a production technology that will have dramatic effects on the biopharmaceutical industry. In the near future, consumers will have access to the first generation of hen-produced drugs and will benefit from the greatly reduced cost as well as increased safety and efficacy of such drugs.

描述（由申请人提供）：基于基因组学的发现和生物技术行业成功实施的基于蛋白质的药物对疾病治疗的影响继续激增。由于需求不断增长和大剂量的需求，蛋白质的产生仍然是一个挑战。许多蛋白质需要翻译后修饰，这些修饰仅由脊椎动物细胞有效地合成。脊椎动物细胞，例如行业标准的中国仓鼠细胞（CHO），在GMP条件下可能很难生长，并且需要巨大的资源来满足市场需求所需的规模。由于维护成本低和易于可伸缩性，动物和植物的生物反应器系统是CHO的有吸引力的替代品。然而，与CHO细胞相比，在动物和植物中，生物药物的翻译后修饰，尤其是糖基化的执行方式不同。由于母鸡的产卵和蛋白质生产能力，这只母鸡被追捕为生物药物生物反应器。已发现与转基因母鸡卵产生的某些蛋白质附着的糖分子与CHO和人类蛋白质共享相同的基本结构。但是，蛋清衍生的糖中缺少一些结构性元素，这对于人类患者的生物活性和生物利用度可能很重要。该项目的目的是遗传工程母鸡，将蛋清像糖结构（如蛋清生物制药）一样赋予完全人类。 公共卫生相关性：拟议的项目，创建具有类似人类特征的人类生物药物的转基因母鸡，将成为生产技术成熟的重要一步，该技术将对生物制药行业产生巨大影响。在不久的将来，消费者将可以使用第一代母鸡生产的药物，并将受益于大大降低的成本以及此类药物的安全性和功效。