| Project/Area Number |
16K12896
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ピロールイミダゾールポリアミド / 人工転写因子 / 金ナノ粒子 / 分化誘導 / 遺伝子・核酸工学材料 / 遺伝子制御分子 / 細胞リプログラミング / 心筋細胞 / ミトコンドリア / 人工ヒストンコード / ナノテクノロジー / リプログラミング |
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| Outline of Final Research Achievements |
Harnessing the chemical biology of nucleic acids, our aim was to successfully carry out bow-arrow reprogramming to achieve clinically useful cell types like cardiomyocytes (CMs) by switching ON and OFF the key transcription factors (TFs) using artificial TFs. We have successfully achieved the first-ever synthetic DNA-binding inhibitor of SOX2, which not only suppressed the pluripotency program in the hiPSCs but also activated the cardiac mesoderm program to generate functional spontaneously contracting CMs when supplemented with a Wnt-signalling inhibitor. Considering the presence of numerous mitochondria in CMs, we also created a ligand for mitochondrial gene modulation. Also, we programmed synthetic molecular codes capable of inducing targeted transcriptional activation of therapeutically important developmental genes in human somatic cells. Current studies with NANO-TFs, the nanoparticle version of synthetic-TFs and distinct bioactive peptides suggest enhanced bioefficacy.
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