Application of Multi-Omics Techniques for Bioprocess Design and Optimization in Chinese Hamster Ovary Cells

Abstract

Significant improvements in the productivity and quality of therapeutic proteins produced in Chinese hamster ovary (CHO) cells have been reported since their establishment as host cells for biopharmaceutical production. Initial advances in the field focused on engineering strategies to manipulate genes associated with proliferation, apoptosis, and various metabolic pathways. Process engineering efforts to optimize culture media, batch-feeding strategies and culture conditions, including temperature and osmolarity, were also reported. More recently, focus has shifted toward enhancing process consistency and product quality using systems biology quality by design-based approaches during process development. Integration of different data generated using omics technologies, such as genomics, transcriptomics, proteomics and metabolomics, has facilitated a greater understanding of CHO cell biology. These techniques have enabled the provision of global information on dynamic changes in cellular components associated with different phenotypes. Using systems biology to understand these important host cells at the cellular level will undoubtedly result in further progression in the development and expression of biopharmaceutical products in CHO cells.

Closed loop control of lactate concentration in mammalian cell culture by Raman spectroscopy leads to improved cell density, viability, and biopharmaceutical protein production

“…Mammalian cell culture is a key technique for the manufacturing of therapeutic proteins which depend on post‐translational modifications for efficacy (Ivarsson et al, ; Ozturk and Hu, ). Culture productivity remains a bottleneck in the production of many therapeutic proteins, and increasing productivity has been the subject of numerous efforts (Dietmair et al, ; Farrell et al, ; Huang et al, ; Lu et al, ; Zalai et al, ). A key limitation of many mammalian cell culture processes is the accumulation of secreted lactate (Lao and Toth, ; Omasa et al, ).…”

Improvements in protein production in mammalian cells from targeted metabolic engineering

“…However, we are still missing fundamental knowledge about how these cellular mechanisms are organized and link together. Furthermore, it is often not clear how they are connected to process conditions, and how these factors all impact protein production [43]. Thus, efforts to further enhance drug production will be facilitated as the molecular basis of these processes are studied and linked to protein production.…”

Proteomics Profiling of Chimeric-Truncated Tissue Plasminogen activator Producing- Chinese Hamster Ovary Cells Cultivated in a Chemically Defined Medium Supplemented with Protein Hydrolysates

“…Industrial applications of CHO cell have motivated researches to improve its expression characteristics, mainly higher specific productivity (q), through cell engineering or culture condition optimization[1-4]. …”