STTR Phase I: Novel bioreactors for production of metabolically engineered heparin in Chinese hamster ovary cells

STTR 第一阶段：用于在中国仓鼠卵巢细胞中生产代谢工程肝素的新型生物反应器

• 批准号: 1321432
• 负责人: Vinit Saxena
• 金额: $ 22.5万
• 依托单位: Sepragen Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1321432&HistoricalAwards=false
• 关键词: STTR; Phase; Novel; bioreactors; production

This Small Business Technology Transfer (STTR) Phase I project proposes to combine a novel metabolically engineered Chinese hamster ovary (CHO) cell line with a unique, high performance, continuous cell-culture bioreactor to demonstrate the commercial viability of producing a bioengineered heparin from CHO cells. This CHO cell line overexpresses critical enzymes in the heparin biosynthesis pathway, resulting in increased levels of a product that is the pharmacological equivalent to heparin. These cells will be grown in the company's proprietary wicking matrix bioreactor that can potentially enable high density, continuously producing cultures in a small footprint, and thus have a multifold reduction in manufacturing cost of goods. The goal is to demonstrate that this engineered CHO cell line can be grown for an extended duration in this bioreactor while maintaining high productivity and product quality. This is expected to be accomplished by optimizing various physical and chemical parameters, developing a unique monitoring system, and continuously assessing metabolic, productivity, and quality attributes associated with heparin production.The broader/commercial impacts of the proposed research, if successful, will be to advance the development of a novel bioreactor system, potentially with a multifold reduction in manufacturing cost of making therapeutics, and the development of a bioengineered heparin, a substantially safer version of a widely used therapeutic. Heparin is the most widely used anticoagulant drug in modern medicine (~$7B) with 100 tons of heparin being produced annually. However, current production methods rely on purification from animal tissues with known and documented deadly incidences of contamination and disease. Achievement of these objectives will have a substantial impact on human health by facilitating the introduction of novel pharmaceuticals in a more cost-effective manner.

这个小型企业技术转移（STTR）I阶段项目建议将新型的代谢中国仓鼠卵巢（CHO）细胞系与独特的高性能，连续的细胞培养物生物反应器结合起来，以证明从CHO细胞中生产生物工程的肝素的商业生存能力。这种CHO细胞系过表达肝素生物合成途径中的临界酶，从而导致产物水平升高，该药物与肝素相当。这些细胞将在该公司专有的芯片基质生物反应器中生长，该基质可以使高密度，不断地产生较小的占地面积，从而降低商品制造成本的多率。目的是证明该生物反应器的这种设计的CHO细胞系可以长时间延长持续时间，同时保持高生产率和产品质量。 This is expected to be accomplished by optimizing various physical and chemical parameters, developing a unique monitoring system, and continuously assessing metabolic, productivity, and quality attributes associated with heparin production.The broader/commercial impacts of the proposed research, if successful, will be to advance the development of a novel bioreactor system, potentially with a multifold reduction in manufacturing cost of making therapeutics, and the development of a bioengineered heparin, a广泛使用的治疗性的基本更安全。肝素是现代医学中使用最广泛的抗凝药物（约7B美元），每年生产100吨肝素。但是，当前的生产方法依赖于已知和记录的污染和疾病致命事件的动物组织的纯化。 实现这些目标将通过以更具成本效益的方式促进新型药品的引入，从而对人类健康产生重大影响。