| Project/Area Number |
16H04572
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biofunction/Bioprocess
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
Yohda Masafumi 東京農工大学, 工学(系)研究科(研究院), 卓越教授 (50250105)
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| Research Collaborator |
Noguchi Keiichi
Shinohara Kyosuke
Fukutani Yosuke
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Keywords | CHO cell / antibody / PDI / Chaperone / シャペロン / プロテインジスルフィドイソメラーゼ / 抗体 / フォールディング / CHO細胞 / 小胞体シャペロン / 小胞体ストレス |
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| Outline of Final Research Achievements |
Therapeutic monoclonal antibodies are produced by mammalian cells, mostly CHO cells, because antibody formation requires intra- and inter-chain disulfide bond formation and glycosylation. Folding and assembly of antibody polypeptide chains take place in the ER. In the antibody-producing plasma cell,Thus, to enhance the antibody production by CHO cell, it seems necessary to improve the folding and assembly system in CHO cells. There exist various PDIs in mammalian cells. However, it is unknown which PDI is responsible for antibody production. When ER stress is induced, expression-level of pdia4 significantly increased in the antibody-producing CHO cell. Knockdown of pdia4 in the antibody-producing CHO cell caused significantly affected the production and maturation of antibody. PDIa4 could assist folding and assembly of the reduced and denatured antibody in vitro. Therefore, we concluded that PDIa4 takes an essential role in the folding and assembly in CHO cells.
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| Academic Significance and Societal Importance of the Research Achievements |
抗体医薬品は使用量が多いため、大量生産技術の開発が課題となっている。低分子化学薬品と比較すると治療に要するコストは高く、その恩恵を得られる人が限られるだけではなく、医療費の高騰という問題も引き起こしている。本研究の成果により、CHO細胞による抗体の生産効率を上げて、生産コストを下げることが期待できる。
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