2020 Fiscal Year Final Research Report
Utilization of chromosomal instability in CHO cells in recombinant protein production
| Project/Area Number |
19K21105
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| Project/Area Number (Other) |
18H05940 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0401:Materials engineering, chemical engineering, and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
Yamano Noriko 大阪大学, 工学研究科, 助教 (20582795)
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| Project Period (FY) |
2018-08-24 – 2021-03-31
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| Keywords | 組換えタンパク質生産 / CHO細胞 / 宿主細胞 / 染色体不安定性 / 染色体不分離 / 染色体異数性 / トランスクリプトーム |
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| Outline of Final Research Achievements |
It was suggested that the amount of mRNA required per amount of protein produced was low in CHO cells with a high chromosome number isolated naturally. From the karyotype analysis, the average number of each chromosome was calculated, and stable chromosomes with low fluctuation values were identified. Next, chromosome aneuploidy was artificially induced and clones with significantly increased chromosome number were isolated. When these cells were tested for production, high productivity tended to be obtained when cells with a high chromosome number were used as a host. When the antibody gene was introduced into the obtained cell line, the specific production rate of the IgG1 antibody was about 65 times higher, that of the IgG3 antibody about 7 times higher, that of the bispecific antibody about 33 times higher, and that of the triple-specific antibody about 3 times higher than when the cell without aneuploidy induction was used as the host.
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| Free Research Field |
生物化学工学
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| Academic Significance and Societal Importance of the Research Achievements |
バイオ医薬品を生産する各製薬企業において、CHO細胞の染色体不安定性への関心は高い。一方で、CHO細胞の染色体の安定性に着目した研究は行われているものの、染色体不安定性を積極的に活用するような研究は行われていない。一言で染色体不安定性とは言え、共通して安定な染色体が存在しており、その不安定性・安定性は染色体毎に異なることが示された。染色体不安定性を誘導、利用しつつ、発現させたい遺伝子はゲノム編集技術を用いて安定な染色体に導入することで、高生産で安定な生産株構築が可能となれば、染色体不安定性を臆することなく、むしろ積極的に利用するという選択肢が増えるのではないかと考える。
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