S115: A Metabolic Model-based Approach to Improve Therapeutic Protein Production in Mammlian Cell Lines

Tuesday, July 26, 2011: 2:00 PM
Bayside BC, 4th fl (Sheraton New Orleans)
Iman Famili1, Renata Usaite1, Adam Feist2, Anne Marie Velasco1 and Jeffrey Rosenbloom1, (1)GT Life Sciences, Inc., San Diego, CA, (2)University of California, San Diego, La Jolla, CA
In a joint collaboration with BGI (formerly known as the Beijing Genomics Institute), we have recently completed sequencing and annotating the CHO genome. The availability of this information is now bringing genome-scale science to CHO-based production of biopharmaceuticals. Using our proprietary computational and experimental platform and genome-scale model of CHO metabolism, we have successfully developed strategies for media optimization and experimentally shown significant increase in product titers and decrease in byproduct accumulation. This modeling approach has also been successfully used to identify metabolically advantageous selectable markers in CHO cells. Genetically engineered CHO cell lines expressing these novel metabolic markers showed higher integrated viable cell density and lower peak byproduct concentrations compared with the parental cell lines. These results demonstrate that metabolic modeling combined with genome-scale technologies can significantly improve and accelerate research, discovery, and development of therapeutic proteins in mammalian cell lines.