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A red light-responsive photoswitch for deep tissue optogenetics
Yuto Kuwasaki1, Kazushi Suzuki1, Gaigai Yu1
1Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
Nature Biotechnology
|June 13, 2022
Summary
Researchers developed MagRed, a novel red light-activated photoswitch for optogenetics. This tool enables precise control of biological processes deep within mammalian tissues, advancing in vivo research capabilities.
Area of Science:
- Optogenetics
- Molecular Biology
- Biochemistry
Background:
- Red light offers advantages for deep tissue penetration and low phototoxicity in optogenetics.
- Development of red light-activated optogenetic tools remains limited, hindering in vivo applications.
Purpose of the Study:
- To engineer a novel red light-activatable photoswitch, named MagRed.
- To demonstrate MagRed's utility for controlling gene expression and DNA recombination in mammalian tissues.
Main Methods:
- Designed MagRed by combining a red light-absorbing bacterial phytochrome with a mammalian endogenous chromophore (biliverdin) and an engineered photo-state-specific binder.
- Utilized Affibody library selection to develop the photo-state-specific binder.
- Fused MagRed components to split-proteins to create light-inducible systems.
Main Results:
- MagRed successfully triggered split-protein assembly upon red light illumination.
- Developed a red light-activatable Cre recombinase enabling deep-tissue DNA recombination.
- Created CRISPR-Cas9-based transcriptional regulators achieving up to 378-fold gene induction.
Conclusions:
- MagRed is a functional red light-activatable photoswitch suitable for deep-tissue optogenetics.
- The developed tools facilitate precise, light-inducible control of genetic processes in vivo.
- MagRed broadens the scope of optogenetic applications in various biological research areas.
