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Title

Applying genome scale metabolic models integrated with OMICs technologies for improvemwent of commercial CHO cell culture process

Authors

Jianlin Xu, Bristol-Myers Squibb Company, USAFollow
Andrew Yongky, Bristol-Myers Squibb Company, USA
Jia Zhao, Bristol-Myers Squibb Company, USA
Nelly Aranibar, Bristol-Myers Squibb Company, USA
Michael Reily, Bristol-Myers Squibb Company, USA
Michael Borys, Bristol-Myers Squibb Company, USA
Zhengjian Li, Bristol-Myers Squibb Company, USA
Seongkyu Yoon, Dept of Chemical Engineering, University of Massachusetts, Lowell, MA
Seoyoung Park, Dept of Chemical Engineering, University of Massachusetts, Lowell, MA
Sha Sha, Dept of Chemical Engineering, University of Massachusetts, Lowell, MA
Zhuangrong Huang, Dept of Chemical Engineering, University of Massachusetts, Lowell, MA

Conference Dates

May 6-11, 2018

Abstract

Although metabolic flux analysis has been established in microbial fermentation, their application in CHO cell culture is sparse. In general CHO cell culture process development is highly rely on empirical experience with limited cell and metabolite data without good mechanism understanding. The purpose of this research is to apply genome scale metabolic modeling for CHO cell culture process improvement. Recently we found that several medium components had significant impact on mAb production by BMSCHO1, a proprietary cell line (Fig. 1). Some of medium components at a low concentration, though within normal ranges for CHO cell culture, caused the BMSCHO1 crashed. Meanwhile some of the other medium components at a low concentration did not cause cell crash, but significantly decreased productivity. The preliminary genetic test results indicated no change in DNA copy number and southern blot integration profile under different medium conditions. Currently we are investigating both supernatant and cell pellets for metabolomics analysis using NMR and LCMS, and assessing epigenetic characteristics. In addition, transcriptomics data have been analyzed by RNA sequence and RT-PCR. Genome-scale modeling integrated with these OMICS datasets have been built and analyzed. In the presentation, we plan to share the investigation details of commercial cell-line and manufacturing process based on the application of genome scale modeling integrated with OMICS technology.

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Recommended Citation

Jianlin Xu, Andrew Yongky, Jia Zhao, Nelly Aranibar, Michael Reily, Michael Borys, Zhengjian Li, Seongkyu Yoon, Seoyoung Park, Sha Sha, and Zhuangrong Huang, "Applying genome scale metabolic models integrated with OMICs technologies for improvemwent of commercial CHO cell culture process" in "Cell Culture Engineering XVI", A. Robinson, PhD, Tulane University R. Venkat, PhD, MedImmune E. Schaefer, ScD, J&J Janssen Eds, ECI Symposium Series, (2018). https://dc.engconfintl.org/ccexvi/172