4.6 Review

Towards translational optogenetics

Journal

NATURE BIOMEDICAL ENGINEERING
Volume 7, Issue 4, Pages 349-369

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41551-021-00829-3

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Optogenetics is a valuable tool for studying neural circuits and therapeutic applications. Future advancements should focus on improving gene delivery vectors, developing red-shifted photoresponsive proteins, enhancing transduction of near-infrared light, and creating wireless implantable light-delivery devices.
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. This Review describes the current optogenetics toolkit, and discusses its preclinical and translational applicability.

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