SBIR Phase II: Development of Bioengineered Anticoagulant Heparin from a Non-Animal Source

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is to eliminate the medical community’s dependence on heparin derived from animal sources. Heparin is an essential anticoagulant drug currently produced from pig intestines, primarily sourced in China. Over 300,000 doses of heparin are administered daily in the US and the global heparin market is valued at $6.5 B. Over the past 12 years, swine diseases that reduced the pig population and limited the amount of heparin available led to economically motivated adulteration and rationing of heparin. Use of heparin derived from pig intestines also results in heparin-induced thrombocytopenia in some patients, which can be reduced via bioengineered heparin. This project advances technology to produce heparin from genetically engineered cells to eliminate the need to source the drug from animals, securing its domestic production. The proposed project pursues increasing the production of bioengineered heparin from cell lines. Previous work has resulted in cell lines that produce material with anticoagulant potency that equals pharmaceutical heparin. The current challenge is to increase yield to meet patient needs at a competitive price. Cells will be genetically engineered to increase their production capacity by overexpressing the enzymes responsible for heparin production. Additionally, the cell culture medium and feeds used to grow the cells, which have been optimized for protein production, will be reformulated to optimize production of heparin in mammalian cells. The objective is to increase the productivity of cells about 100-fold, which will make bioengineered heparin affordable at scale, paving the way for the development of polysaccharide drugs produced from mammalian cells. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.