Using a multi-omics systems biology approach to enhance CHO platform process understanding
July 14-18, 2019
Employing a platform strategy for clone screening and early stage process development can be beneficial not only for shortening process timelines but also for increasing process understanding. By applying the same platform process parameters to different programs with the same host cell line, there are often insights and lessons that can be shared across programs despite differences in the therapeutic protein being produced. This work aims to test and extend this cross-program understanding using a multi-omics systems biology approach, initially incorporating transcriptomics and untargeted metabolomics. By collecting omics samples for the top clones from multiple programs selected in the same platform process, a platform database can be produced to compare the gene expression and metabolite profiles and identify biological pathways that are intrinsically similar, that are clone dependent, and those that are molecule dependent. As a case study, transcriptomic and metabolomic data were collected at multiple time-points from small-scale fed-batch bioreactors for multiple clones producing the same monoclonal antibody. Among these clones, a range of titers, specific productivities, and product quality attributes were observed. By applying the multi-omics approach, there is a potential to identify biological pathways that correlate with unique phenotypes and to then extend these learnings to improve cell culture performance for on-going and future programs.
Laura Leahy, Hima Yalamanchili, Amr Ali, Krishnakumar Malu, and Yizhou Zhou, "Using a multi-omics systems biology approach to enhance CHO platform process understanding" in "Biochemical and Molecular Engineering XXI", Christina Chan, Michigan State University, USA Mattheos Koffas, RPI, USA Steffen Schaffer, Evonik Industries, Germany Rashmi Kshirsagar, Biogen, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/biochem_xxi/39