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.
