earticle

영어

For the production of therapeutic proteins, recombinant Chinese hamster ovary (rCHO) cells have been most widely used in industry. The popularity of rCHO cells is likely to persist as the demand for therapeutic proteins continue to increase. For any commercial process, high volumetric productivity and/or high product titer are desired for the reason of profit. This can be achieved by increasing the specific productivity and/or the time integral of viable cell concentration. Thus, cell engineering has been targeted mainly to increase either one of these factors. When cell engineering is considered, it is critical to understand the intracellular events of cells. For example, apoptotic cell death induced in mild suboptimal conditions is an active, genetically controlled process of cell suicide mediated by the activation of a series of caspases. Therefore, apoptotic cell death can be regulated to some extent by genetic modification. In contrast, necrotic cell death induced at high stress level is a passive, genetically uncontrollable death. Accordingly, overexpression of antiapoptotic gene for extending culture longevity is effective on the condition that cells die mainly by apoptosis, not necrosis. Various strategies such as the overexpression of antiapoptotic genes (mostly bcl-2), down-regulation of effector molecules (caspase-3 and caspase-7), down-regulation of CIRP, overexpression of pyruvate carboxylase, down-regulation of LDH-A, and overexpression of chaperones (ERp57, PDI, calreticulin, and calnexin) have been attempted in our laboratory and efficacy of each CHO cell engineering strategy will be discussed.