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Roadmap for direct and indirect translation of optogenetics into discoveries and therapies for humans.

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Title: Roadmap for direct and indirect translation of optogenetics into discoveries and therapies for humans.
Authors: Lüscher, Christian (AUTHOR), Emiliani, Valentina (AUTHOR), Farahany, Nita (AUTHOR), Gittis, Aryn (AUTHOR), Gradinaru, Viviana (AUTHOR), High, Katherine A. (AUTHOR), Roska, Botond (AUTHOR), Sahel, José-Alain (AUTHOR), Yizhar, Ofer (AUTHOR), Zeng, Hongkui (AUTHOR), Deisseroth, Karl (AUTHOR)
Source: Nature Neuroscience. Dec2025, Vol. 28 Issue 12, p2415-2431. 17p.
Abstract: Optogenetics has transformed basic research on neural circuitry, led to diverse experimental insights into human brain function and dysfunction, and opened pathways for clinical translation based on new understanding of how specific cell types contribute to cognition and behavior. Many of these translational pathways do not rely on the direct application of optogenetics in humans, but rather develop and advance other treatment modalities by leveraging causal knowledge derived from optogenetic circuit neuroscience. However, a recent proof-of-principle study—showing that optogenetics applied directly to the human central nervous system can treat blindness—underscores not only the curative potential but also the need for careful ethical consideration in the extension of direct optogenetic intervention to other disorders. Here, we review relevant considerations—including the selection of clinical indications, identification of molecular and optical strategies for specificity, and navigation of safety and regulatory issues—that together inform the development of optogenetic translation targeting cells and circuits that have been causally implicated through optogenetic discoveries. This Perspective discusses the challenges involved in translating optogenetic research into clinical practice, including clinical and pragmatic choices, potential toxicity and immune responses, regulatory issues and ethical considerations. [ABSTRACT FROM AUTHOR]
Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Roadmap for direct and indirect translation of optogenetics into discoveries and therapies for humans.
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  Data: <searchLink fieldCode="AR" term="%22Lüscher%2C+Christian%22">Lüscher, Christian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Emiliani%2C+Valentina%22">Emiliani, Valentina</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Farahany%2C+Nita%22">Farahany, Nita</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gittis%2C+Aryn%22">Gittis, Aryn</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gradinaru%2C+Viviana%22">Gradinaru, Viviana</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22High%2C+Katherine+A%2E%22">High, Katherine A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Roska%2C+Botond%22">Roska, Botond</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sahel%2C+José-Alain%22">Sahel, José-Alain</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yizhar%2C+Ofer%22">Yizhar, Ofer</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zeng%2C+Hongkui%22">Zeng, Hongkui</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Deisseroth%2C+Karl%22">Deisseroth, Karl</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Nature+Neuroscience%22">Nature Neuroscience</searchLink>. Dec2025, Vol. 28 Issue 12, p2415-2431. 17p.
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  Data: Optogenetics has transformed basic research on neural circuitry, led to diverse experimental insights into human brain function and dysfunction, and opened pathways for clinical translation based on new understanding of how specific cell types contribute to cognition and behavior. Many of these translational pathways do not rely on the direct application of optogenetics in humans, but rather develop and advance other treatment modalities by leveraging causal knowledge derived from optogenetic circuit neuroscience. However, a recent proof-of-principle study—showing that optogenetics applied directly to the human central nervous system can treat blindness—underscores not only the curative potential but also the need for careful ethical consideration in the extension of direct optogenetic intervention to other disorders. Here, we review relevant considerations—including the selection of clinical indications, identification of molecular and optical strategies for specificity, and navigation of safety and regulatory issues—that together inform the development of optogenetic translation targeting cells and circuits that have been causally implicated through optogenetic discoveries. This Perspective discusses the challenges involved in translating optogenetic research into clinical practice, including clinical and pragmatic choices, potential toxicity and immune responses, regulatory issues and ethical considerations. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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