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• W3178706045 abstract "Chinese hamster ovary (CHO) cells present inherent limitations for processing and secretion of large amounts of recombinant proteins, especially for those requiring complex post-translational processing. To tackle these limitations, we engineered CHO host cells (CHOK1 and CHOS) to overexpress the transcription factor BLIMP1/prdm1 (a master regulator of the highly-secreting phenotype of antibody-producing plasma cells), generating novel CHO cell lines (referred to as CHOB). The CHOB cell lines exhibited decreased cell densities, prolonged stationary phase and arrested cell cycle in G1/G0 phase but simultaneously had significantly greater product titre for recombinant IgG1 (> 2-fold increase) coupled with a significantly greater cell-specific productivities (> 3-fold increase). We demonstrated that the improved productive phenotype of CHOB cells resulted from a series of changes to cell physiology and metabolism. CHOB cells showed a significantly greater ER size and increased protein synthesis and secretion capacity compared to control cells. In addition, CHOB cells presented a metabolic profile that favoured energy production to support increased recombinant protein production. This study indicated that a cell engineering approach based on BLIMP1 expression offers great potential for improving the secretory capacity of CHO cell hosts utilised for manufacture of recombinant biopharmaceuticals. Our findings also provides a greater understanding of the relationship between cell growth and productivity, valuable generic information for improving productive phenotypes for CHO cell lines during industrial cell line development." @default.
• W3178706045 created "2021-07-19" @default.
• W3178706045 creator A5022554577 @default.
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• W3178706045 date "2021-09-01" @default.
• W3178706045 modified "2023-10-14" @default.
• W3178706045 title "Overexpression of transcription factor BLIMP1/prdm1 leads to growth inhibition and enhanced secretory capacity in Chinese hamster ovary cells" @default.
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• W3178706045 doi "https://doi.org/10.1016/j.ymben.2021.07.004" @default.
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