旭硝子財団助成研究成果報告2022

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斎藤　進50Susumu SAITO藤本　健造51Kenzo FUJIMOTO光照射下でも頑健な分子触媒の構造基盤構築とCO2資源化への展開（2016採択)Development of Structurally Robust Molecular Catalysts under Light: Application to CO2 immobilization as Carbon Resources(Project 2016)細胞内ゲノムDNA及びRNAを標的とした光化学的なピンポイント塩基編集による遺伝子治療法の開発(2018採択)Development of ultrafast photo-cross-linking mediated cellular DNA and RNA editing from C to U (Project 2018)48旭硝子財団　助成研究成果報告（2022）学術界や産業界を問わず枯渇資源の代替と補完が世界で模索されている．今後の人口増加にも伴い，エネルギーと資源の持続性の確保と多様化の促進は緊急の課題である．また枯渇資源のみに依存し続ける限りCO2の排出は避けることができない．一方でCO2は枯渇しない炭素資源として有望である．例えば，CO2を還元することで，工業的な原料である一酸化炭素（CO）や，水素貯蔵や燃料電池への応用が期待されているギ酸（HCO2H）など様々な有用化合物が得られる．この考えのもと本研究では，光エネルギーを用いるCO2の資源化法の開発に新規な金属錯体触媒の創出を通じて挑む．新しい「光に対して頑健な金属錯体」に関わる分子設計概念を導入し活用できれば，光による二量化や構造分解による触媒失活を防ぐことができ，高効率で持続可能なCO2還元系を構築できる．The recent depletion of fossil fuel resources has impelled industrial and academic researchers to search for alternative carbon sources. Developing sustainable resources/energy is one of the most urgent missions for human beings since the increasing resources/energy deamnd is in drastic conflict with the limited global fossil fuels storage. In particular, massive production of CO2 is inevitable and the fatal risk as far as fossil resources are continuously used as the only sources of carbon. This project will develop novel transition metal complex photocatalysts for CO2 reduction as a part of the attempt to mitigate CO2 risk, in which CO2 could be re-duced, via electron/hydrogen transfer, to value-added chemicals such as HCO2H and CO using light energy. When using light energy, the main issue is how to keep the structural robustness of molecular photocatalysts to realize high and sustainable catalyst performance since transition metal complex catalysts coordinated with organic ligand frameworks are frequently decomposed/dimerized to inactive species upon light irradiation.光化学的核酸塩基編集法は，光応答性人工塩基を含む修飾核酸による可逆的な光架橋を用いてピンポイントでDNA及びRNA上のシトシン（C）をウラシル（U）へと変換する方法である．本研究では，細胞内でも操作可能な新規光応答性人工核酸の開発を行い，まずRNAを標的とした光化学的核酸塩基編集を試み，脱アミノ化効率に対する標的シトシンの周囲環境の影響を明らかにした．次に細胞内での時空間制御可能な光化学的RNA編集法の確立を試みた．またゲノム操作法のために必要と考えられる光誘導DNAダブルストランドインベージョン（Photo-induced DNA Double-strand Invasion: pDDI）法の確立も試みた．Photochemical nucleobase editing is a method of pinpointing the conversion of cytosine (C) to uracil (U) on DNA and RNA using reversible photocross-linking with modified nucleic acids containing photoresponsive artificial bases. In this study, we developed a novel photoresponsive artificial nucleic acid that can be manip-ulated intracellularly. We first attempted photochemical nucleobase editing targeting RNA, and clarified the effect of the surrounding environment on the deamination efficiency of the target cytosine. Next, we attempt-ed to establish an intracellular, spatiotemporally controllable photochemical RNA editing method. We also