Zinc supplementation increases protein titer of recombinant CHO cells.
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ABSTRACT: In order to study the impact of zinc and copper on the titer levels of mAb and recombinant protein in CHO cells, the IgG-expressing (DP12) and EPO-expressing (SK15) cell lines were cultured in chemically defined media with increasing concentrations of either metal. Supplementation with 25 mg/l in CDM media resulted in a significant increase in EPO (1.7-fold) and IgG (2.6-fold) titers compared to control (no added zinc). Titers at this Zn concentration in CDM containing the insulin replacing agent aurintricarboxylic acid (ATA) (CDM?+?A) showed a 1.8-fold (EPO) and 1.2-fold (IgG) titers increase compared to control. ATA appeared to also reduce the specific productivity (Qp) enhancement induced by Zn-25, with up to 4.9-fold (DP12) and 1.9-fold (SK15) Qp increase in CDM compared to the 1.6-fold (DP12) and 1.5-fold (SK15) Qp increase observed in CDM?+?A. A 31% reduced Viable Cell Density (VCD) in DP12 was observed in both Zn-supplemented media (3?×?106 cells/ml vs 4.2?×?106 cells/ml, day 5), whereas SK15 Zn-25 cultures displayed a 24% lower peak only in CDM?+?A (2.2?×?106 cells/ml vs 3.2?×?106 cells/ml, day 5). Supplementation with copper at 13.7-20 mg/l resulted in less significant cell line/product-type dependent effects on titer, VCD and Viability. Analysis of the energetic phenotype of both cell lines in 25 mg/l Zn-supplemented CDM media revealed a twofold increase in the oxygen consumption rate (OCR) compared to non-supplemented cells. Together, these data suggest that high zinc supplementation may induce an increase in oxidative respiration metabolism that results in increased Qp and titers in suspension CHO cultures.
SUBMITTER: Capella Roca B
PROVIDER: S-EPMC6787129 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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