2023 Fiscal Year Final Research Report
Development of organoid gene analysis system elucidating individual differences in cancer.
| Project/Area Number |
22K19575
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
SEKINE KEISUKE 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (00323569)
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| Project Period (FY) |
2022-06-30 – 2024-03-31
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| Keywords | 癌オルガノイド |
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| Outline of Final Research Achievements |
We constructed a model system by introducing a gene expressing the fluorescent protein BFP into primary cancer cells and performing a genetic modification where a single amino acid substitution in BFP converts its fluorescence to GFP. Using this model system, we conducted studies and achieved a few percent gene modification efficiency. Firstly, we considered gene introduction for recombination to be a hurdle. Therefore, we explored gene delivery methods such as electroporation, gene delivery reagents, and introduction using Adeno-Associated Virus (AAV) vectors, and compared gene modification efficiencies using PrimeEditor.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
癌の個性は遺伝子変異に加え、ゲノム背景や癌細胞の細胞特性に起因すると考えられるため、患者由来のプライマリ癌細胞が利用されるようになってきている。次世代シークエンス解析の発展により、VUS（Variants of Uncertain Significance）と呼ばれる臨床的意義不明のバリアントが多く見つかっており、VUSの機能解析を実施する為にはin vitroで操作可能な癌オルガノイドを対象とした効率の良い遺伝子改変技術の開発が不可欠であり、本研究ではVUSの機能解析に向けたゲノム編集技術の効率化検討が実施され、将来的な癌治療に向けた基礎研究の基盤になると期待される。
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