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  • Review Article
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Towards translational optogenetics

Nature Biomedical Engineering volume 7, pages 349–369 (2023)Cite this article

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Abstract

Optogenetics is widely used to interrogate the neural circuits underlying disease and has most recently been harnessed for therapeutic applications. The optogenetic toolkit consists of light-responsive proteins that modulate specific cellular functions, vectors for the delivery of the transgenes that encode the light-responsive proteins to targeted cellular populations, and devices for the delivery of light of suitable wavelengths at effective fluence rates. A refined toolkit with a focus towards translational uses would include efficient and safer viral and non-viral gene-delivery vectors, increasingly red-shifted photoresponsive proteins, nanomaterials that efficiently transduce near-infrared light deep into tissue, and wireless implantable light-delivery devices that allow for spatiotemporally precise interventions at clinically relevant tissue depths. In this Review, we examine the current optogenetics toolkit and the most notable preclinical and translational uses of optogenetics, and discuss future methodological and translational developments and bottlenecks.

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Fig. 1: Light-responsive proteins.
Fig. 2: The translational optogenetics toolkit.
Fig. 3: Targeted gene delivery.
Fig. 4: Red-shifted photoreceptors.
Fig. 5: Wireless light-delivery approaches.
Fig. 6: Light transducers in optogenetics.

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Acknowledgements

We thank the Ministry of Education of Singapore (MOE), Tier3 and Tier1 programme (MOE 2016-T3-1-004, R-397-000-274-112, R-397-000-348-114, R-397-000-375-114); the National Medical Research Council (NMRC/OFIRG/0071/2018, R-397-000-317-213, MOH-000640, R-397-000-386-213); and the National University of Singapore for financial support.

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  1. These authors contributed equally: Akshaya Bansal, Swati Shikha.

Authors and Affiliations

  1. Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore

    Akshaya Bansal, Swati Shikha & Yong Zhang

  2. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore

    Yong Zhang

  3. NUS Suzhou Research Institute, Suzhou, Jiangsu, P. R. China

    Yong Zhang

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Y.Z., A.B. and S.S. conceived the project. A.B. and S.S. performed the literature review and wrote the manuscript draft. Y.Z., A.B. and S.S. discussed the content and revised the manuscript.

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Correspondence to Yong Zhang.

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Bansal, A., Shikha, S. & Zhang, Y. Towards translational optogenetics. Nat. Biomed. Eng 7, 349–369 (2023). https://doi.org/10.1038/s41551-021-00829-3

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