Assessment of cell engineering strategies for improved therapeutic protein production in CHO cells

Abstract

Recombinant glycoprotein therapeutics have proven to be invaluable pharmaceuticals for the treatment of various diseases. Chinese hamster ovary (CHO) cells are widely used in industry for the production of these proteins. Several strategies for engineering CHO cells for improved protein production have been tried with considerable results. The focus has mainly been to increase the specific productivity and to extend the culture longevity by preventing programmed cell death. These CHO cell engineering strategies, particularly those developed in Korea, are reviewed here.

Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

“…This multitude of studies showing positive effects clearly underpins the potential of modulating the expression of effector genes. However, as previously pointed out (Hussain et al, 2014;Kim et al, 2012;Mohan et al, 2008), some effector genes are flawed by inconsistent effects. To exemplify this, all published studies on rprotein productivity (volumetric productivity or q p ) in CHO cells with the ectopic expression of the widely studied protein disulphide isomerase (PDI) are listed in Table 1.…”

A proteomic approach for identifying cellular proteins interacting with erythropoietin in recombinant Chinese hamster ovary cells

“…1,[16][17][18] Thus, the screening of specific binding and helper proteins which improve the foreign protein production by a pull-down assay in combination with proteomic analysis is an important step in cell engineering. EPO, which is one of the most important therapeutic proteins produced in rCHO cells, was chosen as a model foreign protein.…”

“…1 It can therefore be inferred that foreign proteins might exist as incompletely folded and unfolded forms in rCHO cells. Identification of the cellular proteins interacting with incompletely folded and unfolded forms of foreign protein in rCHO cells could eventually lead to a better insight into possible genetic manipulation approaches for increasing foreign protein production.…”

Mammalian cells as biopharmaceutical production hosts in the age of omics

“…Mammalian cells as biopharmaceutical production hosts in the age of omics crease the rate of proliferation, enhance proteinprocessing capacity, and increase metabolic efficiency [2][3][4]. However the outcome of these manipulation has been mixed [5], with only a few studies reporting significant improvements in productivity.…”