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.

该小企业技术转让（STTR）I期项目拟将新型代谢工程化中国仓鼠卵巢（CHO）细胞系与独特的高性能连续细胞培养生物反应器相结合，以证明从CHO细胞生产生物工程化肝素的商业可行性。该CHO细胞系过度表达肝素生物合成途径中的关键酶，导致与肝素药理学等效的产物水平升高。这些细胞将在该公司专有的芯吸矩阵生物反应器中生长，该生物反应器可能实现高密度，在小占地面积内连续生产培养物，从而成倍降低商品的制造成本。目的是证明该工程化CHO细胞系可在该生物反应器中生长较长时间，同时保持高生产率和产品质量。这有望通过优化各种物理和化学参数，开发独特的监测系统，并持续评估与肝素生产相关的代谢，生产力和质量属性来实现。如果成功，拟议研究的更广泛/商业影响将是推进新型生物反应器系统的开发，可能使治疗剂的制造成本降低数倍，以及生物工程肝素的开发，这是一种广泛使用的治疗药物的安全性更高的版本。肝素是现代医学中使用最广泛的抗凝药物（约70亿美元），每年生产100吨肝素。然而，目前的生产方法依赖于从动物组织中纯化，这些动物组织具有已知的和记录在案的致命的污染和疾病发生率。 这些目标的实现将通过促进以更具成本效益的方式引进新的药物而对人类健康产生重大影响。