| 研究課題/領域番号 |
20K07604
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分50010:腫瘍生物学関連
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| 研究機関 | 国立研究開発法人理化学研究所 |
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研究代表者 |
Gailhouste Luc 国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (40848537)
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| 研究期間 (年度) |
2020-04-01 – 2023-03-31
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| 研究課題ステータス |
交付 (2021年度)
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| 配分額 *注記 |
3,900千円 (直接経費: 3,000千円、間接経費: 900千円)
2022年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2021年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円)
2020年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | microRNA / Epigenome editing / Tumor-suppressor / DNA methylation / dCas9-Tet1 / MicroRNAs / epigenome editing / tumor-suppressor / cancer |
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| 研究開始時の研究の概要 |
1. Apr. to Dec. 2020: in silico analysis and design of the gRNAs. Challenge of targeted epigenome editing and demethylation of the candidate tumor-suppressor miRNAs in cancer cells.
2. Jan. to June 2021: assessment of the recovery of tumor-suppressor activities mediated by the reactivation of the miRNAs.
3. July 2021 to June 2022: tumor growth models (in vivo).
4. July 2022 to March 2023: compilation of the data, analyses, manuscript writing, submission, and potential revision
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| 研究実績の概要 |
The objective of this project was to develop a reliable system for targeted demethylation and reactivation of specific cancer-related microRNAs (miRNAs). By adapting the CRISPR-Cas9 system and establishing an innovative editing technology, we have been able to accurately manipulate the epigenome of tumor-suppressor miRNAs for functional analyses and potential therapeutic applications. Thus far, the following aims have been achieved:
1. Targeted demethylation of the tumor-suppressor miR-122 using the dCas9-TET1 epigenome editing system
2. Identification of miR-122 targets using miRNA epigenome editing
3. miR-122 editing negatively impacts hepatic cancer cell growth through SLC2A3 targeting
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
This work is currently in progress as expected. Tumor-suppressor miRNA epigenome editing using animal experimental models will be achieved this year.
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| 今後の研究の推進方策 |
We are currently applying targeted demethylation of miRNAs to other types of tumor cells, especially pancreatic ductal adenocarcinoma cells. Importantly, reactivation of tumor-suppressor miRNAs other than miR-122 is in progress to demonstrate the versatility of our miRNA epigenome editing system. Further functional analyses will help to clarify interactions between the edited miRNAs and their potential targets. Last, mouse tumor growth models will be used to validate the therapeutic potential of miRNA epigenome editing.
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