The relationship of metabolic burden to productivity levels in CHO cell lines

The growing demand for recombinant therapeutics has driven biotechnologists to develop new production strategies. One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell‐specific productivity through environmental perturbations. In this work, the effect...

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Veröffentlicht in:Biotechnology and applied biochemistry 2018-03, Vol.65 (2), p.173-180
Hauptverfasser: Zou, Wu, Edros, Raihana, Al‐Rubeai, Mohamed
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creator Zou, Wu
Edros, Raihana
Al‐Rubeai, Mohamed
description The growing demand for recombinant therapeutics has driven biotechnologists to develop new production strategies. One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell‐specific productivity through environmental perturbations. In this work, the effects of hypothermia, hyperosmolarity, high shear stress, and sodium butyrate treatment on growth and productivity were studied using three (low, medium, and high producing) CHO cell lines that differed in their specific productivities of monoclonal antibody. In all three cell lines, the inhibitory effect of these parameters on proliferation was demonstrated. Additionally, compared to the control, specific productivity was enhanced under all conditions and exhibited a consistent cell line specific pattern, with maximum increases (50–290%) in the low producer, and minimum increases (7–20%) in the high producer. Thus, the high‐producing cell line was less responsive to environmental perturbations than the low‐producing cell line. We hypothesize that this difference is most likely due to the bottleneck associated with a higher metabolic burden caused by higher antibody expression. Increased recombinant mRNA levels and pyruvate carboxylase activities due to low temperature and hyperosmotic stress were found to be positively associated with the metabolic burden.
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One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell‐specific productivity through environmental perturbations. In this work, the effects of hypothermia, hyperosmolarity, high shear stress, and sodium butyrate treatment on growth and productivity were studied using three (low, medium, and high producing) CHO cell lines that differed in their specific productivities of monoclonal antibody. In all three cell lines, the inhibitory effect of these parameters on proliferation was demonstrated. Additionally, compared to the control, specific productivity was enhanced under all conditions and exhibited a consistent cell line specific pattern, with maximum increases (50–290%) in the low producer, and minimum increases (7–20%) in the high producer. Thus, the high‐producing cell line was less responsive to environmental perturbations than the low‐producing cell line. 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source Wiley Journals
subjects Biotechnology
Cell lines
environmental perturbation
Gene expression
GS‐CHO cell line
Hypothermia
Low temperature
metabolic burden
Metabolism
Monoclonal antibodies
monoclonal antibody
mRNA
Osmotic pressure
Productivity
Proteins
Pyruvate carboxylase
Pyruvic acid
Shear stress
Sodium
Sodium butyrate
specific productivity
title The relationship of metabolic burden to productivity levels in CHO cell lines
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