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Inducible transgene expression in CHO cells using an artificial transcriptional activator with estrogen-binding domain
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  • Md. Rashidur Rahman,
  • Yoshinori Kawabe,
  • Kozumi Suzuki,
  • Satoshi Chen,
  • Yuki Amamoto,
  • Masamichi Kamihira
Md. Rashidur Rahman
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Yoshinori Kawabe
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Kozumi Suzuki
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Satoshi Chen
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Yuki Amamoto
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Masamichi Kamihira
Kyushu University

Corresponding Author:[email protected]

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Biopharmaceuticals, including therapeutic antibodies, are rapidly growing products in the pharmaceutical market. Mammalian cells, such as Chinese hamster ovary (CHO) cells, are widely used as production hosts because recombinant antibodies require complex three-dimensional structures modified with sugar chains. Recombinant protein production using mammalian cells is generally performed in conjunction with cell growth. In this study, we developed a technology that controls cell growth and recombinant protein production to induce recombinant protein production with arbitrary timing. Expression of green fluorescent protein (GFP) gene and a single-chain antibody fused with the Fc-region of the human IgG1 (scFv-Fc) gene can be induced and mediated by the estrogen receptor-based artificial transcription factor Gal4-ERT2-VP16 and corresponding inducer drugs. We generated CHO cells using an artificial gene expression system. The addition of various concentrations of inducer drugs to the culture medium allowed control of proliferation and transgene expression of the engineered CHO cells. Use of 4-hydroxytamoxifen, an antagonist of estrogen, as an inducing agent yielded high gene expression at a concentration more than 10-fold lower than that of β-estradiol. When scFv-Fc was continuously produced under inducing conditions, stable production was possible for more than 2 weeks while maintaining high specific productivity (57 pg cell-1 day-1). This artificial gene expression control system that utilizes the estrogen response of estrogen receptors can be an effective method for inducible production of biopharmaceuticals.
26 Jul 2023Submitted to Biotechnology Journal
26 Jul 2023Submission Checks Completed
26 Jul 2023Assigned to Editor
02 Aug 2023Reviewer(s) Assigned
25 Oct 2023Review(s) Completed, Editorial Evaluation Pending
31 Oct 2023Editorial Decision: Revise Major
09 Nov 20231st Revision Received
10 Nov 2023Submission Checks Completed
10 Nov 2023Assigned to Editor
10 Nov 2023Review(s) Completed, Editorial Evaluation Pending
10 Nov 2023Reviewer(s) Assigned
22 Nov 2023Editorial Decision: Revise Major