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Overexpression of CHOP alone and in combination with chaperones is effective in improving antibody production in mammalian cells

  • Applied Genetics and Molecular Biotechnology
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Abstract

Secretory capacities including folding and assembly are believed to be limiting factors in the establishment of mammalian cell lines producing high levels of recombinant therapeutic proteins. To achieve industrial success, it is also important to improve protein folding, assembly, and secretory processes in combination with increasing transcription and translation. Here, we identified the expression of CHOP/Gadd153 and GRP78, which are unfolded protein response (UPR)-related genes, correlated with recombinant antibody production in stable CHO cells. Subsequently, CHOP overexpression resulted in increasing recombinant antibody production in some mammalian cell lines, and in addition a threefold further enhancement was obtained by combining expression with UPR-related genes or ER chaperones in transient assays. Overexpression of CHOP had no effect on the biochemical characteristics of the product. These results suggest overexpression of CHOP and its combinations may be an effective method to efficiently select a single cell line with a high level of antibody production in the development of cell lines for manufacturing.

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Authors and Affiliations

  1. R&D Division, Biologics Research Laboratories, DAIICHISANKYO CO., LTD., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan

    Daisuke Nishimiya & Tohru Takahashi

  2. Pharmaceutical Technology Division, Biopharmaceutical Technology Research Laboratories, DAIICHISANKYO CO., LTD., 2716-1 Kurakake, Akaiwa, Chiyoda-machi, Ohura-gun, Gunma, 370-0503, Japan

    Takashi Mano & Kenji Miyadai

  3. R&D Division, R&D Planning Department, DAIICHISANKYO CO., LTD., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan

    Hiroko Yoshida

Authors
  1. Daisuke Nishimiya
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  2. Takashi Mano
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  3. Kenji Miyadai
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  4. Hiroko Yoshida
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  5. Tohru Takahashi
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Correspondence to Daisuke Nishimiya.

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Nishimiya, D., Mano, T., Miyadai, K. et al. Overexpression of CHOP alone and in combination with chaperones is effective in improving antibody production in mammalian cells. Appl Microbiol Biotechnol 97, 2531–2539 (2013). https://doi.org/10.1007/s00253-012-4365-9

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  • DOI: https://doi.org/10.1007/s00253-012-4365-9

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