2色の光で人工細胞を制御―「必要な時に、必要な分だけ」働く分子ロボットで、未来のピンポイント治療へ― (Controlling Artificial Cells with Two Colors of Light Using Molecular Robots That Act Only When and Where Needed)

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2026-10-07 東北大学

東北大学などの研究グループは、人工細胞(GUV)内のmRNA量を、青色光と紫外線という2種類の光で可逆的に増減させる分子システムを開発した。光で構造が変化するアゾベンゼンをDNAに組み込み、mRNAの「合成」と「切断」を切り替える仕組みを構築。青色光ではDNAが安定な構造となり転写が進んでmRNAが増加し、紫外線では構造が変化して転写を抑制するとともに、RNase HによるmRNA切断を誘導して量を減少させる。実際に人工細胞内で、光照射に応じたmRNA濃度の可逆的な増減を確認した。これは従来の「作る」制御に加えて「壊す」制御も組み込んだもので、必要な場所・時刻・量だけ分子を生成する分子ロボットやピンポイント治療への応用が期待される。

2色の光で人工細胞を制御―「必要な時に、必要な分だけ」働く分子ロボットで、未来のピンポイント治療へ― (Controlling Artificial Cells with Two Colors of Light Using Molecular Robots That Act Only When and Where Needed)
図1. 光に応答してmRNA濃度を制御する人工細胞。

<関連情報>

人工細胞内におけるmRNA濃度切り替えのためのmRNA合成および切断の可逆的光制御 Reversible Photocontrol of mRNA Synthesis and Cleavage for mRNA Concentration Switching Inside Artificial Cells

Daichi Iwata, Keiji Murayama, Ken Komiya, Hideaki T. Matsubayashi, Keita Abe, Hiroyuki Asanuma, Satoshi Murata, Shin-ichiro M. Nomura
ChemSystemsChem  Published: 17 September 2026
DOI:https://doi.org/10.1002/syst.70057

ABSTRACT

Spatiotemporal control of gene expression in response to external stimuli is a crucial technology in cell-free gene expression (CFE) and artificial cells. Most conventional control methods have focused on switching transcription ON/OFF. However, residual mRNA can persist after transcription stops, leading to continued gene expression. Active mechanisms that decrease mRNA levels are effective for achieving a sharp OFF response. Here, we report a method using azobenzene-modified hairpin DNA (AzoPinDNA) and RNase H to simultaneously and reversibly control transcription and RNA cleavage. AzoPinDNA modulates RNase H-mediated mRNA cleavage by photo-switching its duplex formation capability. Notably, we confirmed that AzoPinDNA controls both RNA cleavage and transcription. Our system achieved reversible control with a dynamic range of 2–3-fold for intact mRNA and 3.5–6.5-fold for peptide products. A rapid OFF response was realized, reducing mRNA concentration by over 50% within 20 min after UV irradiation. Furthermore, this system functioned within artificial cells (giant unilamellar vesicles), enabling external photocontrol of the concentration of translatable mRNA within the compartment. This approach, which integrally photocontrols both transcription and mRNA cleavage, represents the first method for manipulating mRNA levels at will. Applications in synthetic biology and basic medicine are anticipated.

生物化学工学
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