Enhancement of the glycosylation machinery of the hen bioreactor

描述（由申请人提供）：在基因组学的发现和生物技术行业的成功实施的推动下，基于蛋白质的药物在疾病治疗中的影响继续激增。由于对大剂量的需求和需要不断增加，蛋白质的生产仍然是一个挑战。许多蛋白质需要翻译后修饰，而这些修饰只能由脊椎动物细胞有效合成。脊椎动物细胞，例如工业标准的中国人脊椎动物细胞（CHO），可能难以在GMP条件下生长，并且需要大量资源来以满足市场需求所需的规模繁殖。基于动物和植物的生物反应器系统是CHO的有吸引力的替代方案，因为其维护成本低且易于扩展。然而，与CHO细胞相比，生物药物的翻译后修饰，特别是糖基化，在动物和植物中以不同的方式进行。母鸡，因为其多产的产卵和蛋白质生产能力，已被追求作为生物制药生物反应器。已经发现，附着在转基因母鸡的蛋中产生的某些蛋白质上的糖分子与CHO和人类蛋白质具有相同的基本结构。然而，蛋清衍生的糖中缺乏一些结构元素，这些结构元素对人类患者的生物活性和生物利用度可能很重要。该项目的目标是对母鸡进行基因工程改造，使其在蛋清衍生的生物药物上具有完全类似人类的糖结构。 公共卫生相关性：拟议的项目，创造转基因母鸡，生产具有人类特征的人类生物药物，将是生产技术成熟的重要一步，将对生物制药行业产生巨大影响。在不久的将来，消费者将有机会获得第一代母鸡生产的药物，并将受益于大大降低的成本以及这些药物的安全性和有效性的提高。

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.