Enhancement of the glycosylation machinery of the hen bioreactor

描述(申请人提供)：在基因组学发现和生物技术行业成功实施的推动下，以蛋白质为基础的药物在疾病治疗中的影响继续激增。蛋白质的生产仍然是一个挑战，因为对大剂量的需求和需求不断增加。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地合成。脊椎动物细胞，如行业标准的中国仓鼠细胞(CHO)，在GMP条件下很难生长，需要巨大的资源才能满足市场需求所需的规模繁殖。动植物生物反应器系统由于维护成本低，易于扩展，是CHO的一种有吸引力的替代方案。然而，与CHO细胞相比，生物药物的翻译后修饰，特别是糖基化，在动物和植物中执行的方式不同。这种母鸡由于其多产的产蛋和蛋白质生产能力，一直被用作生物制药生物反应器。在转基因母鸡的鸡蛋中产生的某些蛋白质上附着的糖分子被发现与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，这些元素可能对人类患者的生物活性和生物利用度很重要。该项目的目标是对母鸡进行基因工程，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。 与公共健康相关：拟议的项目是创造转基因母鸡，生产具有类似人类特征的人类生物药物，这将是生产技术成熟的重要一步，这将对生物制药行业产生巨大影响。在不久的将来，消费者将能够获得第一代母鸡生产的药物，并将受益于此类药物的成本大幅降低以及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.