Curated Optogenetic Publication Database

Search precisely and efficiently by using the advantage of the hand-assigned publication tags that allow you to search for papers involving a specific trait, e.g. a particular optogenetic switch or a host organism.

Showing 26 - 50 of 345 results
Review
26.

Optogenetics Sheds Light on Brown and Beige Adipocytes.

blue BLUF domains Review
J Cell Signal, 2023 DOI: 10.33696/signaling.4.105 Link to full text
Abstract: Excessive food intake leads to lipid accumulation in white adipose tissue, triggering inflammation, cellular stress, insulin resistance, and metabolic syndrome. In contrast, the dynamic energy expenditure and heat generation of brown and beige adipose tissue, driven by specialized mitochondria, render it an appealing candidate for therapeutic strategies aimed at addressing metabolic disorders. This review examines the therapeutic potential of brown and beige adipocytes for obesity and metabolic disorders, focusing on recent studies that employ optogenetics for thermogenesis control in these cells. The findings delve into the mechanisms underlying UCP1-dependent and UCP1-independent thermogenesis and how optogenetic approaches can be used to precisely modulate energy expenditure and induce thermogenesis. The convergence of adipocyte biology and optogenetics presents an exciting frontier in combating metabolic disorders and advancing our understanding of cellular regulation and energy balance.
27.

Multiomics and optobiotechnological approaches for the development of microalgal strain for production of aviation biofuel and biorefinery.

blue Cryptochromes Review
Bioresour Technol, 9 Dec 2022 DOI: 10.1016/j.biortech.2022.128457 Link to full text
Abstract: Demand and consumption of fossil fuels is increasing daily, and oil reserves are depleting. Technological developments are required towards developing sustainable renewable energy sources and microalgae are emerging as a potential candidate for various application-driven research. Molecular understanding attained through omics and system biology approach empowering researchers to modify various metabolic pathways of microalgal system for efficient extraction of biofuel and important biomolecules. This review furnish insight into different "advanced approaches" like optogenetics, systems biology and multi-omics for enhanced production of FAS (Fatty Acid Synthesis) and lipids in microalgae and their associated challenges. These new approaches would be helpful in the path of developing microalgae inspired technological platforms for optobiorefinery, which could be explored as source material to produce biofuels and other valuable bio-compounds on a large scale.
28.

Precise modulation of embryonic development through optogenetics.

blue cyan violet BLUF domains Cryptochromes Fluorescent proteins LOV domains Review
Genesis, 7 Dec 2022 DOI: 10.1002/dvg.23505 Link to full text
Abstract: The past decade has witnessed enormous progress in optogenetics, which uses photo-sensitive proteins to control signal transduction in live cells and animals. The ever-increasing amount of optogenetic tools, however, could overwhelm the selection of appropriate optogenetic strategies. In this work, we summarize recent progress in this emerging field and highlight the application of opsin-free optogenetics in studying embryonic development, focusing on new insights gained into optical induction of morphogenesis, cell polarity, cell fate determination, tissue differentiation, neuronal regeneration, synaptic plasticity, and removal of cells during development.
29.

Light-regulated gene expression in Bacteria: Fundamentals, advances, and perspectives.

blue green near-infrared red violet BLUF domains Cobalamin-binding domains Cryptochromes Cyanobacteriochromes LOV domains Phytochromes Review
Front Bioeng Biotechnol, 14 Oct 2022 DOI: 10.3389/fbioe.2022.1029403 Link to full text
Abstract: Numerous photoreceptors and genetic circuits emerged over the past two decades and now enable the light-dependent i.e., optogenetic, regulation of gene expression in bacteria. Prompted by light cues in the near-ultraviolet to near-infrared region of the electromagnetic spectrum, gene expression can be up- or downregulated stringently, reversibly, non-invasively, and with precision in space and time. Here, we survey the underlying principles, available options, and prominent examples of optogenetically regulated gene expression in bacteria. While transcription initiation and elongation remain most important for optogenetic intervention, other processes e.g., translation and downstream events, were also rendered light-dependent. The optogenetic control of bacterial expression predominantly employs but three fundamental strategies: light-sensitive two-component systems, oligomerization reactions, and second-messenger signaling. Certain optogenetic circuits moved beyond the proof-of-principle and stood the test of practice. They enable unprecedented applications in three major areas. First, light-dependent expression underpins novel concepts and strategies for enhanced yields in microbial production processes. Second, light-responsive bacteria can be optogenetically stimulated while residing within the bodies of animals, thus prompting the secretion of compounds that grant health benefits to the animal host. Third, optogenetics allows the generation of precisely structured, novel biomaterials. These applications jointly testify to the maturity of the optogenetic approach and serve as blueprints bound to inspire and template innovative use cases of light-regulated gene expression in bacteria. Researchers pursuing these lines can choose from an ever-growing, versatile, and efficient toolkit of optogenetic circuits.
30.

Recent Synthetic Biology Approaches for Temperature- and Light-Controlled Gene Expression in Bacterial Hosts.

blue UV LOV domains UV receptors Review
Molecules, 11 Oct 2022 DOI: 10.3390/molecules27206798 Link to full text
Abstract: The expression of genes of interest (GOI) can be initiated by providing external stimuli such as temperature shifts and light irradiation. The application of thermal or light stimuli triggers structural changes in stimuli-sensitive biomolecules within the cell, thereby inducing or repressing gene expression. Over the past two decades, several groups have reported genetic circuits that use natural or engineered stimuli-sensitive modules to manipulate gene expression. Here, we summarize versatile strategies of thermosensors and light-driven systems for the conditional expression of GOI in bacterial hosts.
31.

The status and challenges of optogenetic tools for precise spatiotemporal control of RNA metabolism and function.

blue Cryptochromes LOV domains Review
Clin Transl Med, Oct 2022 DOI: 10.1002/ctm2.1078 Link to full text
Abstract: Abstract not available.
32.

Creating artificial signaling gradients to spatially pattern engineered tissues.

blue Cryptochromes Review
Curr Opin Biotechnol, 28 Sep 2022 DOI: 10.1016/j.copbio.2022.102810 Link to full text
Abstract: Artificially constructing a fully-fledged tissue - comprising multiple cell types whose identities and spatial arrangements reflect those of a native tissue - remains daunting. There has been impressive progress in generating three-dimensional cell cultures (often dubbed 'organoids') from stem cells. However, it is critical to appreciate that not all such three-dimensional cultures will intrinsically self-organize to spontaneously recreate native tissue architecture. Instead, most tissues in vivo are exogenously patterned by extracellular signaling gradients emanating from organizer cells located outside the tissue. Innovations to impose artificial signaling gradients - using microfluidics, optogenetics, or introducing organizer cells - could thus prove decisive to create spatially patterned tissues in vitro. Additionally, unified terminology to describe these tissue-like simulacra as 'aggregates', 'spheroids', or 'organoids' will be critical for the field.
33.

Proteomic mapping and optogenetic manipulation of membrane contact sites.

blue Cryptochromes LOV domains Review
Biochem J, 16 Sep 2022 DOI: 10.1042/bcj20220382 Link to full text
Abstract: Membrane contact sites (MCSs) mediate crucial physiological processes in eukaryotic cells, including ion signaling, lipid metabolism, and autophagy. Dysregulation of MCSs is closely related to various diseases, such as type 2 diabetes mellitus (T2DM), neurodegenerative diseases, and cancers. Visualization, proteomic mapping and manipulation of MCSs may help the dissection of the physiology and pathology MCSs. Recent technical advances have enabled better understanding of the dynamics and functions of MCSs. Here we present a summary of currently known functions of MCSs, with a focus on optical approaches to visualize and manipulate MCSs, as well as proteomic mapping within MCSs.
34.

Ligand-independent receptor clustering modulates transmembrane signaling: a new paradigm.

blue red Cryptochromes LOV domains Phytochromes Review
Trends Biochem Sci, 14 Sep 2022 DOI: 10.1016/j.tibs.2022.08.002 Link to full text
Abstract: Cell-surface receptors mediate communication between cells and their environment. Lateral membrane organization and dynamic receptor cluster formation are fundamental in signal transduction and cell signaling. However, it is not yet fully understood how receptor clustering modulates a wide variety of physiologically relevant processes. Recent growing evidence indicates that biological responses triggered by membrane receptors can be modulated even in the absence of the natural receptor ligand. We review the most recent findings on how ligand-independent receptor clustering can regulate transmembrane signaling. We discuss the latest technologies to control receptor assembly, such as DNA nanotechnology, optogenetics, and optochemistry, focusing on the biological relevance and unraveling of ligand-independent signaling.
35.

The bright frontiers of microbial metabolic optogenetics.

blue green red Cryptochromes Cyanobacteriochromes LOV domains Phytochromes Review
Curr Opin Chem Biol, 11 Sep 2022 DOI: 10.1016/j.cbpa.2022.102207 Link to full text
Abstract: In recent years, light-responsive systems from the field of optogenetics have been applied to several areas of metabolic engineering with remarkable success. By taking advantage of light's high tunability, reversibility, and orthogonality to host endogenous processes, optogenetic systems have enabled unprecedented dynamical controls of microbial fermentations for chemical production, metabolic flux analysis, and population compositions in co-cultures. In this article, we share our opinions on the current state of this new field of metabolic optogenetics.We make the case that it will continue to impact metabolic engineering in increasingly new directions, with the potential to challenge existing paradigms for metabolic pathway and strain optimization as well as bioreactor operation.
36.

Nano-optogenetic immunotherapy.

blue Cryptochromes LOV domains Review
Clin Transl Med, Sep 2022 DOI: 10.1002/ctm2.1020 Link to full text
Abstract: Chimeric antigen receptor (CAR) T cell-based immunotherapy has been increasingly used in the clinic for cancer intervention over the past 5 years. CAR T-cell therapy takes advantage of genetically-modified T cells to express synthetic CAR molecules on the cell surface. To date, up to six CAR T cell therapy products have been approved by the Food and Drug Administration for the treatment of leukaemia, lymphoma, and multiple myeloma. In addition, hundreds of CAR-T products are currently under clinical trials to treat solid tumours. In both the fundamental research and clinical applications, CAR T cell immunotherapy has achieved exciting progress with remarkable remission or suppression of cancers. However, CAR T cell-based immunotherapy still faces significant safety issues, as exemplified by "on-target off-tumour" cytotoxicity due to lack of strict antigen specificity. In addition, uncontrolled massive activation of infused CAR T cells may create severe systemic inflammation with cytokine release syndrome and neurotoxicity. These challenges call for a need to combine nanotechnology and optogenetics with immunoengineering to develop spatiotemporally-controllable CAR T cells, which enable wireless photo-tunable activation of therapeutic immune cells to deliver personalised therapy in the tumour microenvironment.
37.

Shedding light on current trends in molecular optogenetics.

blue green red violet BLUF domains Cobalamin-binding domains Cryptochromes Fluorescent proteins LOV domains Phytochromes Review
Curr Opin Chem Biol, 18 Aug 2022 DOI: 10.1016/j.cbpa.2022.102196 Link to full text
Abstract: Molecular optogenetics is a highly dynamic research field. In the past two years, the field was characterized by the development of new allosteric switches as well as the forward integration of optogenetics research towards application. Further, two areas of research have significantly gathered momentum, the use of optogenetics to control liquid-liquid phase separation as well as the application of optogenetic tools in the extracellular space. Here, we review these areas and discuss future directions.
38.

Illuminating bacterial behaviors with optogenetics.

blue green red violet BLUF domains Cryptochromes Cyanobacteriochromes LOV domains Phytochromes Review
Curr Opin Solid State Mater Sci, 9 Aug 2022 DOI: 10.1016/j.cossms.2022.101023 Link to full text
Abstract: Optogenetic approaches enable light-mediated control of cellular activities using genetically encoded photoreceptors. While optogenetic technology is already well established in neuroscience and fundamental research, the implementation of optogenetic tools in bacteriology is still emerging. Engineered bacteria with the specific optogenetic system that function at the transcriptional or post-translational level can sense and respond to light, allowing optogenetic control of bacterial behaviors. In this review, we give a brief overview of available optogenetic systems, including their mode of action, classification, and engineering strategies, and focus on optogenetic control of bacterial behaviors with the highlight of strategies for use of optogenetic systems.
39.

Optogenetics for light control of biological systems

blue red BLUF domains Cryptochromes LOV domains Phytochromes Review
Nat Rev Methods Primers, 21 Jul 2022 DOI: 10.1038/s43586-022-00149-z Link to full text
Abstract: The H2 + H2 system has long been considered a benchmark system for ro-vibrational energy transfer in bimolecular collisions. However, most studies thus far have focused on collisions involving H2 molecules in the ground vibrational level or in the first excited vibrational state. While H2 + H2/HD collisions have received wide attention due to the important role they play in astrophysics, D2 + D2 collisions have received much less attention. Recently, Zhou et al. [ Nat. Chem. 2022, 14, 658-663, DOI: 10.1038/s41557-022-00926-z] examined stereodynamic aspects of rotational energy transfer in collisions of two aligned D2 molecules prepared in the v = 2 vibrational level and j = 2 rotational level. Here, we report quantum calculations of rotational and vibrational energy transfer in collisions of two D2 molecules prepared in vibrational levels up to v = 2 and identify key resonance features that contribute to the angular distribution in the experimental results of Zhou et al. The quantum scattering calculations were performed in full dimensionality and using the rigid-rotor approximation using a recently developed highly accurate six-dimensional potential energy surface for the H4 system that allows descriptions of collisions involving highly vibrationally excited H2 and its isotopologues.
40.

Emerging molecular technologies for light-mediated modulation of pancreatic beta-cell function.

blue red BLUF domains LOV domains Phytochromes Review
Mol Metab, 19 Jul 2022 DOI: 10.1016/j.molmet.2022.101552 Link to full text
Abstract: Optogenetic modalities as well as optochemical and photopharmacological strategies, collectively termed optical methods, have revolutionized the control of cellular functions via light with great spatiotemporal precision. In comparison to the major advances in the photomodulation of signaling activities noted in neuroscience, similar applications to endocrine cells of the pancreas, particularly insulin-producing β-cells, have been limited. The availability of tools allowing light-mediated changes in the trafficking of ions such as K+ and Ca2+ and signaling intermediates such as cyclic adenosine monophosphate (cAMP), renders β-cells and their glucose-stimulated insulin secretion (GSIS) amenable to optoengineering for drug-free control of blood sugar.
41.

Recent advances in cellular optogenetics for photomedicine.

blue cyan green near-infrared red UV violet PhyB/PIF6 BLUF domains Cobalamin-binding domains Cryptochromes Fluorescent proteins LOV domains Phytochromes UV receptors Review
Adv Drug Deliv Rev, 16 Jul 2022 DOI: 10.1016/j.addr.2022.114457 Link to full text
Abstract: Since the successful introduction of exogenous photosensitive proteins, channelrhodopsin, to neurons, optogenetics has enabled substantial understanding of profound brain function by selectively manipulating neural circuits. In an optogenetic system, optical stimulation can be precisely delivered to brain tissue to achieve regulation of cellular electrical activity with unprecedented spatio-temporal resolution in living organisms. In recent years, the development of various optical actuators and novel light-delivery techniques has greatly expanded the scope of optogenetics, enabling the control of other signal pathways in non-neuronal cells for different biomedical applications, such as phototherapy and immunotherapy. This review focuses on the recent advances in optogenetic regulation of cellular activities for photomedicine. We discuss emerging optogenetic tools and light-delivery platforms, along with a survey of optogenetic execution in mammalian and microbial cells.
42.

Engineering of optogenetic devices for biomedical applications in mammalian synthetic biology.

blue near-infrared red UV violet BLUF domains Cryptochromes Fluorescent proteins LOV domains Phytochromes UV receptors Review
Eng Biol, 7 Jul 2022 DOI: 10.1049/enb2.12022 Link to full text
Abstract: Gene- and cell-based therapies are the next frontiers in the field of medicine. Both are transformative and innovative therapies; however, a lack of safety data limits the translation of such promising technologies to the clinic. Improving the safety and promoting the clinical translation of these therapies can be achieved by tightly regulating the release and delivery of therapeutic outputs. In recent years, the rapid development of optogenetic technology has provided opportunities to develop precision-controlled gene- and cell-based therapies, in which light is introduced to precisely and spatiotemporally manipulate the behaviour of genes and cells. This review focuses on the development of optogenetic tools and their applications in biomedicine, including photoactivated genome engineering and phototherapy for diabetes and tumours. The prospects and challenges of optogenetic tools for future clinical applications are also discussed.
43.

Plant optogenetics: Applications and perspectives.

blue cyan green near-infrared red UV Cobalamin-binding domains Cryptochromes Cyanobacteriochromes Fluorescent proteins LOV domains Phytochromes UV receptors Review
Curr Opin Plant Biol, 30 Jun 2022 DOI: 10.1016/j.pbi.2022.102256 Link to full text
Abstract: To understand cell biological processes, like signalling pathways, protein movements, or metabolic processes, precise tools for manipulation are desired. Optogenetics allows to control cellular processes by light and can be applied at a high temporal and spatial resolution. In the last three decades, various optogenetic applications have been developed for animal, fungal, and prokaryotic cells. However, using optogenetics in plants has been difficult due to biological and technical issues, like missing cofactors, the presence of endogenous photoreceptors, or the necessity of light for photosynthesis, which potentially activates optogenetic tools constitutively. Recently developed tools overcome these limitations, making the application of optogenetics feasible also in plants. Here, we highlight the most useful recent applications in plants and give a perspective for future optogenetic approaches in plants science.
44.

Optogenetics for transcriptional programming and genetic engineering.

blue cyan near-infrared red UV violet Cryptochromes Fluorescent proteins LOV domains Phytochromes UV receptors Review
Trends Genet, 20 Jun 2022 DOI: 10.1016/j.tig.2022.05.014 Link to full text
Abstract: Optogenetics combines genetics and biophotonics to enable noninvasive control of biological processes with high spatiotemporal precision. When engineered into protein machineries that govern the cellular information flow as depicted in the central dogma, multiple genetically encoded non-opsin photosensory modules have been harnessed to modulate gene transcription, DNA or RNA modifications, DNA recombination, and genome engineering by utilizing photons emitting in the wide range of 200-1000 nm. We present herein generally applicable modular strategies for optogenetic engineering and highlight latest advances in the broad applications of opsin-free optogenetics to program transcriptional outputs and precisely manipulate the mammalian genome, epigenome, and epitranscriptome. We also discuss current challenges and future trends in opsin-free optogenetics, which has been rapidly evolving to meet the growing needs in synthetic biology and genetics research.
45.

Extracellular Optogenetics at the Interface of Synthetic Biology and Materials Science.

blue cyan green red UV violet Cobalamin-binding domains Cryptochromes Fluorescent proteins LOV domains Phytochromes UV receptors Review
Front Bioeng Biotechnol, 14 Jun 2022 DOI: 10.3389/fbioe.2022.903982 Link to full text
Abstract: We review fundamental mechanisms and applications of OptoGels: hydrogels with light-programmable properties endowed by photoswitchable proteins ("optoproteins") found in nature. Light, as the primary source of energy on earth, has driven evolution to develop highly-tuned functionalities, such as phototropism and circadian entrainment. These functions are mediated through a growing family of optoproteins that respond to the entire visible spectrum ranging from ultraviolet to infrared by changing their structure to transmit signals inside of cells. In a recent series of articles, engineers and biochemists have incorporated optoproteins into a variety of extracellular systems, endowing them with photocontrollability. While other routes exist for dynamically controlling material properties, light-sensitive proteins have several distinct advantages, including precise spatiotemporal control, reversibility, substrate selectivity, as well as biodegradability and biocompatibility. Available conjugation chemistries endow OptoGels with a combinatorially large design space determined by the set of optoproteins and polymer networks. These combinations result in a variety of tunable material properties. Despite their potential, relatively little of the OptoGel design space has been explored. Here, we aim to summarize innovations in this emerging field and highlight potential future applications of these next generation materials. OptoGels show great promise in applications ranging from mechanobiology, to 3D cell and organoid engineering, and programmable cell eluting materials.
46.

Optogenetic technologies in translational cancer research.

blue cyan green near-infrared red Cryptochromes Cyanobacteriochromes Fluorescent proteins LOV domains Phytochromes Review
Biotechnol Adv, 9 Jun 2022 DOI: 10.1016/j.biotechadv.2022.108005 Link to full text
Abstract: Gene and cell therapies are widely recognized as future cancer therapeutics but poor controllability limits their clinical applications. Optogenetics, the use of light-controlled proteins to precisely spatiotemporally regulate the activity of genes and cells, opens up new possibilities for cancer treatment. Light of specific wavelength can activate the immune response, oncolytic activity and modulate cell signaling in tumor cells non-invasively, in dosed manner, with tissue confined action and without side effects of conventional therapies. Here, we review optogenetic approaches in cancer research, their clinical potential and challenges of incorporating optogenetics in cancer therapy. We critically discuss beneficial combinations of optogenetic technologies with therapeutic nanobodies, T-cell activation and CAR-T cell approaches, genome editors and oncolytic viruses. We consider viral vectors and nanoparticles for delivering optogenetic payloads and activating light to tumors. Finally, we highlight herein the prospects for integrating optogenetics into immunotherapy as a novel, fast, reversible and safe approach to cancer treatment.
47.

Platforms for Optogenetic Stimulation and Feedback Control.

blue green red Cryptochromes Cyanobacteriochromes Phytochromes Review
Front Bioeng Biotechnol, 8 Jun 2022 DOI: 10.3389/fbioe.2022.918917 Link to full text
Abstract: Harnessing the potential of optogenetics in biology requires methodologies from different disciplines ranging from biology, to mechatronics engineering, to control engineering. Light stimulation of a synthetic optogenetic construct in a given biological species can only be achieved via a suitable light stimulation platform. Emerging optogenetic applications entail a consistent, reproducible, and regulated delivery of light adapted to the application requirement. In this review, we explore the evolution of light-induction hardware-software platforms from simple illumination set-ups to sophisticated microscopy, microtiter plate and bioreactor designs, and discuss their respective advantages and disadvantages. Here, we examine design approaches followed in performing optogenetic experiments spanning different cell types and culture volumes, with induction capabilities ranging from single cell stimulation to entire cell culture illumination. The development of automated measurement and stimulation schemes on these platforms has enabled researchers to implement various in silico feedback control strategies to achieve computer-controlled living systems-a theme we briefly discuss in the last part of this review.
48.

Tools for studying the cytoskeleton during plant cell division.

blue LOV domains Review
Trends Plant Sci, 3 Jun 2022 DOI: 10.1016/j.tplants.2022.05.006 Link to full text
Abstract: The plant cytoskeleton regulates fundamental biological processes, including cell division. How to experimentally perturb the cytoskeleton is a key question if one wants to understand the role of both actin filaments (AFs) and microtubules (MTs) in a given biological process. While a myriad of mutants are available, knock-out in cytoskeleton regulators, when nonlethal, often produce little or no phenotypic perturbation because such regulators are often part of a large family, leading to functional redundancy. In this review, alternative techniques to modify the plant cytoskeleton during plant cell division are outlined. The different pharmacological and genetic approaches already developed in cell culture, transient assays, or in whole organisms are presented. Perspectives on the use of optogenetics to perturb the plant cytoskeleton are also discussed.
49.

Synthetic microbiology applications powered by light.

blue green red BLUF domains Cyanobacteriochromes LOV domains Phytochromes Review
Curr Opin Microbiol, 31 May 2022 DOI: 10.1016/j.mib.2022.102158 Link to full text
Abstract: Synthetic biology is a field of research in which molecular parts (mostly nucleic acids and proteins) are de novo created or modified and then used either alone or in combination to achieve new functions that can help solve the problems of our modern society. In synthetic microbiology, microbes are employed rather than other organisms or cell-free systems. Optogenetics, a relatively recently established technology that relies on the use of genetically encoded photosensitive proteins to control biological processes with high spatiotemporal precision, offers the possibility to empower synthetic (micro)biology applications due to the many positive features that light has as an external trigger. In this review, we describe recent synthetic microbiology applications that made use of optogenetics after briefly introducing the molecular mechanism behind some of the most employed optogenetic tools. We highlight the power and versatility of this technique, which opens up new horizons for both research and industry.
50.

The expanding role of split protein complementation in opsin-free optogenetics.

blue green near-infrared red violet BLUF domains Cobalamin-binding domains Cryptochromes Fluorescent proteins LOV domains Phytochromes Review
Curr Opin Pharmacol, 21 May 2022 DOI: 10.1016/j.coph.2022.102236 Link to full text
Abstract: A comprehensive understanding of signaling mechanisms helps interpret fundamental biological processes and restore cell behavior from pathological conditions. Signaling outcome depends not only on the activity of each signaling component but also on their dynamic interaction in time and space, which remains challenging to probe by biochemical and cell-based assays. Opsin-based optogenetics has transformed neural science research with its spatiotemporal modulation of the activity of excitable cells. Motivated by this advantage, opsin-free optogenetics extends the power of light to a larger spectrum of signaling molecules. This review summarizes commonly used opsin-free optogenetic strategies, presents a historical overview of split protein complementation, and highlights the adaptation of split protein recombination as optogenetic sensors and actuators.
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