Near‐Infrared Optogenetic Genome Engineering Based on Photon‐Upconversion Hydrogels

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  • Yoichi Sasaki
    Department of Chemistry and Biochemistry Graduate School of Engineering Center for Molecular Systems (CMS) Kyushu University 744 Moto-oka, Nishi-ku Fukuoka 819-0395 Japan
  • Mio Oshikawa
    Center for Brain Integration Research (CBIR) Tokyo Medical and Dental University (TMDU) 1-5-45 Yushima, Bunkyo-ku Tokyo 113–8510 Japan
  • Pankaj Bharmoria
    Department of Chemistry and Biochemistry Graduate School of Engineering Center for Molecular Systems (CMS) Kyushu University 744 Moto-oka, Nishi-ku Fukuoka 819-0395 Japan
  • Hironori Kouno
    Department of Chemistry and Biochemistry Graduate School of Engineering Center for Molecular Systems (CMS) Kyushu University 744 Moto-oka, Nishi-ku Fukuoka 819-0395 Japan
  • Akiko Hayashi‐Takagi
    Laboratory of Medical Neuroscience Institute for Molecular and Cellular Regulation Gunma University Maebashi-city Gunma 371-8512 Japan
  • Moritoshi Sato
    Graduate School of Arts and Sciences The University of Tokyo, Komaba, Meguro-ku Tokyo 153-8902 Japan
  • Itsuki Ajioka
    Center for Brain Integration Research (CBIR) Tokyo Medical and Dental University (TMDU) 1-5-45 Yushima, Bunkyo-ku Tokyo 113–8510 Japan
  • Nobuhiro Yanai
    Department of Chemistry and Biochemistry Graduate School of Engineering Center for Molecular Systems (CMS) Kyushu University 744 Moto-oka, Nishi-ku Fukuoka 819-0395 Japan
  • Nobuo Kimizuka
    Department of Chemistry and Biochemistry Graduate School of Engineering Center for Molecular Systems (CMS) Kyushu University 744 Moto-oka, Nishi-ku Fukuoka 819-0395 Japan

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<jats:title>Abstract</jats:title><jats:p>Photon upconversion (UC) from near‐infrared (NIR) light to visible light has enabled optogenetic manipulations in deep tissues. However, materials for NIR optogenetics have been limited to inorganic UC nanoparticles. Herein, NIR‐light‐triggered optogenetics using biocompatible, organic TTA‐UC hydrogels is reported. To achieve triplet sensitization even in highly viscous hydrogel matrices, a NIR‐absorbing complex is covalently linked with energy‐pooling acceptor chromophores, which significantly elongates the donor triplet lifetime. The donor and acceptor are solubilized in hydrogels formed from biocompatible Pluronic F127 micelles, and heat treatment endows the excited triplets in the hydrogel with remarkable oxygen tolerance. Combined with photoactivatable Cre recombinase technology, NIR‐light stimulation successfully performs genome engineering resulting in the formation of dendritic‐spine‐like structures of hippocampal neurons.</jats:p>

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