Volume 58, Issue 49 pp. 17827-17833
Research Article

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

Yoichi Sasaki

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

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Dr. Mio Oshikawa

Dr. Mio Oshikawa

Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113–8510 Japan

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Dr. Pankaj Bharmoria

Dr. 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

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Hironori Kouno

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

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Prof. Akiko Hayashi-Takagi

Prof. Akiko Hayashi-Takagi

Laboratory of Medical Neuroscience, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi-city, Gunma, 371-8512 Japan

PRESTO, JST, Honcho 4-1-8, Kawaguchi, Saitama, 332-0012 Japan

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Prof. Moritoshi Sato

Prof. Moritoshi Sato

Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo, 153-8902 Japan

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Prof. Itsuki Ajioka

Corresponding Author

Prof. Itsuki Ajioka

Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113–8510 Japan

PRESTO, JST, Honcho 4-1-8, Kawaguchi, Saitama, 332-0012 Japan

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Prof. Nobuhiro Yanai

Corresponding Author

Prof. 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

PRESTO, JST, Honcho 4-1-8, Kawaguchi, Saitama, 332-0012 Japan

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Prof. Nobuo Kimizuka

Corresponding Author

Prof. 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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First published: 23 September 2019
Citations: 142

Graphical Abstract

Near-infrared (NIR) light-triggered optogenetics with triplet–triplet annihilation-based photon upconversion (TTA-UC) is demonstrated. Triplet-lifetime extension by the covalent conjugation of donor and acceptor and a heat-induced conformational change of the hydrogel that prevents oxygen diffusion enables the formation of dendritic-spine-like structures by hippocampal neurons, induced by NIR-to-blue TTA-UC.

Abstract

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.

Conflict of interest

The authors declare no conflict of interest.

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