| Project/Area Number |
18K19513
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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 52:General internal medicine and related fields
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| Research Institution | Mie University |
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Principal Investigator |
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | ダウン症 / トリソミックレスキュー / 小核 / 染色体消去 / Cas9 / ダウン症候群 / トリソミー / CRISPR/Cas / iPS細胞 / 染色体 |
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| Outline of Final Research Achievements |
Identification of small nuclear migration trigger protein, since it was difficult to separate the small nuclear-specific protein by two-dimensional electrophoresis, specifically cleavage the target chromosome using CRISPR / Cas9, after the transition to a small nucleus, it was changed to a strategy to induce acquired trisomic rescue. Most disomy cells appeared in 13 cleavage, it is believed that acquired trisomic rescue was induced. In the future, it is necessary to further confirm the reproducibility, double-stranded cut target chromosome, the frequency of migration and decomposition to the small nucleus can not be dna repair is increased, it is presumed that acquired trisomic rescue was able to induce as a result. Currently, for these induced disomy cells, detailed analysis such as STR analysis and MLPA method is being carried out.
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| Academic Significance and Societal Importance of the Research Achievements |
標的染色体１本のみを切断し、小核へ移行・分解させることにより、後天的にトリソミックレスキューを誘導することが出来た。この結果から、ダウン症候群を始めとする染色体異数性の根本的治療、またはがん遺伝子治療の新規治療方法の開発に新たな可能性が広がったと考える。まだ効率やドラッグデリバリーシステム等の課題はあるが、標的染色体を小核に移行させることが有用な手法となりうる。今後は、切断箇所の数の追加による効率化、切断箇所の組み合わせ最適化、エクソソームを用いた標的細胞特異的な核型修正、最終的にはDNA二本鎖の切断を用いない方法を構築し、臨床応用に近づけたい。
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