Attenuating apoptosis in Chinese hamster ovary cells for improved biopharmaceutical production
Matthew Henry, M. A. MacDonald, Camila A. Orellana, Peter P. Gray, Marianne Gillard, Kym Baker, Lars K. Nielsen, Esteban Marcellin, Stephen M. Mahler, Verónica S. Martínez
Abstract
Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by-products, and mechanical shear, hindering production. Genetic engineering strategies to reduce apoptosis in CHO cells have been investigated with mixed results. In this review, a contemporary understanding of the real complexity of apoptotic mechanisms and signaling pathways is described; followed by an overview of antiapoptotic cell line engineering strategies tested so far in CHO cells.