STTR Phase I: Biomanufacture of Novel Heparan Sulfate Glycosaminoglycans

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project will be to commercialize novel sugar polymers known as glycosaminoglycan (GAGs) for a variety of important medical applications. GAGs are key components in a number of important physiologic and pathophysiologic conditions (e.g., tumor angiogenesis, thrombosis); however, developing a detailed understanding of these roles, which may significantly impact human health, is challenging due to a lack of analytical techniques for glycan analysis and the absence of high quality GAG samples available for research. GAGs have precise functional roles in cell signaling cascades, which can vary depending on the particular GAG structural composition. Particular GAG compositions vary among different tissue types as well as among different developmental and physiological states. Hence, to achieve the proper functional characteristics and obtain reproducible experimental results, it is critical that GAG samples are available with consistent and defined compositions. Unfortunately, most commercially available GAG samples are from animal sources with high inherent variability and are not well characterized. The potential for contamination or adventitious agents makes the animal-derived GAG samples even less desirable for human therapeutics. This STTR Phase I project proposes to develop genetically engineered Chinese Hamster Ovary (CHO) cells producing GAGs with defined compositions. Culture conditions will be optimized to maintain GAG composition while providing product yields at a level sufficient for commercialization. A series of engineered cell lines will be produced in order to prepare GAGs with different compositions that model the different compositions and different functional characteristics found in nature. GAG samples will be characterized both structurally and functionally to provide profiles for each type of sample, which will be reliable and reproducible since the GAGs are prepared from cells grown under controlled conditions. These samples will be a valuable resource for researchers in a number of biological and medical fields. It is thought that the high quality will command premium prices. However, to help reduce costs and promote commercialization, this proposal will test growth conditions in bioreactors to increase the capacity and efficiency of production. Research using these high quality GAG samples will provide proof-of-principal for the use these GAGs in a variety of important therapeutic applications such as oncology, lipid metabolism, tissue regeneration, and hematology.