2021 Fiscal Year Annual Research Report
心筋症関連ミトコンドリア・核内遺伝子の協奏的制御を可能にする人工転写因子の開発
| Project/Area Number |
19H03349
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
杉山 弘 京都大学, 理学研究科, 教授 (50183843)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | ピロールイミダゾールポリアミド / エピジェネティクス / 人工転写因子 / ナノテクノロジー / 心筋症 |
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| Outline of Annual Research Achievements |
In this fiscal year, we accomplished the milestones mentioned in the proposal and have further broadened the applicability of functional nanomaterials in uncharted domains of precision medicine. First, we have shown that our advanced biomimetic epigenetic codes could operate as smart transcription factors (SMART-TFs) and artificially regulate nuclear genes associated with mitochondrial biogenesis and cellular energy metabolism. This nucleus targeting SMART-TF synergized with PD-1 blockade to enhance antitumor immunity and improve host survival. We also developed nanoparticle-based selective mitochondria targeting Mito-SMART-TF with high colloidal stability, outstanding biocompatibility, efficient cell uptake, and amenability to be monitored in live cells using near-infrared fluorescence. Both the nuclear and mitochondrial SMART-TFs demonstrated the individual capacity of altering the redox status of the live cells by regulating the reactive oxygen species (ROS) production. Also, we harnessed our transcription therapeutic strategy to construct a multi-functional conjugate capable of sequence-specific adenine alkylation and published the demonstration of targeted elimination of mutated mitochondrial DNA in HeLa cells. Furthermore, we have developed 1) chemical probe-based nanopore direct RNA sequencing approach to accurately assess the RNA modifications and 2) enhanced the bioapplicability of self-enclosed microfluidic devices to be used for pore-sized separation of biomolecular mixtures. These results are published and/or to be published in high impact research journals.
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| Research Progress Status |
令和3年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和3年度が最終年度であるため、記入しない。
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