Integrating data intelligence and hybrid modelling to develop continuous CHO cell lines for recombinant protein production

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Developing sustainable bio-manufacturing technologies for industrial production of pharmaceuticals is a top priority in growing and advancing the UK's Bioeconomy. Chinese hamster ovary (CHO) cells are the leading production platform for manufacturing protein-based therapeutics, as they possess the appropriate machinery for the synthesis and processing of proteins with large molecular structures and complex humanlike post-translational modifications. However, a significant limitation of CHO cells as a manufacturing platform is their deficient secretory phenotype which leads to protein production that compares unfavourably to cells with a dedicated secretory machinery. To enable overexpression of target recombinant proteins and improve process performance of CHO cell lines at larger manufacturing scales, it is of critical importance to investigate the biological mechanisms and overcome the intrinsic limitations of the underlying bioprocess at each level from intracellular metabolism to bioreactor operation through a whole-systems approach.