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A small and highly sensitive red/far-red optogenetic switch for applications in mammals
Yang Zhou1, Deqiang Kong1, Xinyi Wang1
1Synthetic Biology and Biomedical Engineering Laboratory, Biomedical Synthetic Biology Research Center, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
We developed REDMAP, a miniaturized optogenetic system using red/far-red light for precise biological control. This compact tool enables rapid, spatiotemporal regulation of cellular processes and gene expression in vivo, with potential therapeutic applications.
Area of Science:
- Optogenetics
- Molecular Biology
- Systems Biology
Background:
- Current optogenetic systems face limitations in size, complexity, illumination requirements, and kinetics.
- There is a need for more efficient and versatile optogenetic tools for in vivo applications.
Purpose of the Study:
- To develop a miniaturized, red/far-red light-mediated optogenetic system.
- To demonstrate the broad applicability of this new system for controlling biological processes in vivo.
Main Methods:
- Developed the REDMAP (red/far-red light-mediated and miniaturized Δphytochrome A-based photoswitch) system using plant photoreceptor PhyA and shuttle protein FHY1.
- Applied REDMAP for dynamic control of MAPK signaling, CRISPR-dCas9-mediated epigenetic remodeling, and transgene expression in animal models.
- Utilized red/far-red light illumination (660 nm and 730 nm) for rapid activation and deactivation.
Main Results:
- Demonstrated rapid binding and dissociation of REDMAP components under specific light wavelengths.
- Successfully controlled endogenous Ras/Erk MAPK cascade and epigenetic modifications in mice.
- Showcased in vivo applications in mice, rats, and rabbits, including transgene expression and regulation of glucose homeostasis in diabetic models.
Conclusions:
- REDMAP is a compact, sensitive, and rapid optogenetic tool for precise spatiotemporal control of biological activities.
- The system shows significant potential for basic research and therapeutic interventions in animals.
- REDMAP offers advantages over existing optogenetic technologies due to its miniaturization and efficiency.
