Towards next generation CHO cell line development and engineering by systems approaches

Chinese hamster ovary (CHO) cells are the most prevalent mammalian cell factories for producing therapeutic biologics, due to its capacity for complex post-translational modifications, ability to grow well in suspension cultures and low susceptibility to human viral infections. Significant advances in various modules of the CHO cell line development and engineering (CLD&E) have contributed to up to 100-fold increase in the product yields over the last three decades. Although production yield still remains the major focus in CLD&E, product quality and long-term stability have increasingly appeared to be the additional criteria. Towards achieving such goals, various platforms involving high-throughput clonal evaluation in automated manner, efficient vector designs, RNA interference methods and genome editing techniques have been developed to generate highly productive clones much faster with desired quality attributes and cell line traits. Since CHO genome was sequenced, we can now systematically characterize CHO cells using high-throughput omics profiles and in silico computational models, thereby identifying relevant targets for rational cell engineering which can be readily validated by the emerging genome editing techniques in a targeted and precise manner. In this review, we summarize the history of CHO CLD&E, and then describe the major technological advancements along with the application areas. Lastly, our perspectives on the next generation CLD&E are provided within the context of mammalian systems biotechnology.