Abstract
Recombinant Chinese hamster ovary cells (rCHO) cells have been the most commonly used mammalian host for large-scale commercial production of therapeutic proteins. Recent advances in cell culture technology for rCHO cells have achieved significant improvement in protein production leading to titer of more than 10 g/L to meet the huge demand from market needs. This achievement is associated with progression in the establishment of high and stable producer and the optimization of culture process including media development. In this review article, we focus on current strategies and achievements in cell line development, mainly in vector engineering and cell engineering, for high and stable protein production in rCHO cells. The approaches that manipulate various DNA elements for gene targeting by site-specific integration and cis-acting elements to augment and stabilize gene expression are reviewed here. The genetic modulation strategy by “direct” cell engineering with growth-promoting and/or productivity-enhancing factors and omics-based approaches involved in transcriptomics, proteomics, and metabolomics to pursue cell engineering are also presented.
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This research was supported in part by the World Class University program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST, R31-2008-000-10071-0), the Converging Research Center Program through the NRF funded by the MEST (2009–0082276), and a grant from the Fundamental R&D Program for Technology of World Premier Materials funded by the Ministry of Knowledge Economy, Republic of Korea.
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Kim, J.Y., Kim, YG. & Lee, G.M. CHO cells in biotechnology for production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol 93, 917–930 (2012). https://doi.org/10.1007/s00253-011-3758-5
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DOI: https://doi.org/10.1007/s00253-011-3758-5