Curated Optogenetic Publication Database

Abstract: Tumor recurrence, metastasis, and therapeutic resistance remain major challenges in oncology, driving the need for advanced therapeutic strategies with improved precision and controllability. Optogenetics, which enables light-mediated regulation of cellular functions, has emerged as a promising modality for cancer therapy by offering unparalleled spatiotemporal precision. This capability allows dynamic control of intracellular signaling and transgene expression, enabling selective targeting of malignant cells while minimizing damage to surrounding tissues. However, clinical translation is hindered by key challenges, including inefficient in vivo delivery of optogenetic components, limited tissue penetration of activating light, and suboptimal performance of existing tools. Addressing these barriers requires a convergence of molecular engineering and materials science, wherein advanced biomaterials play a critical role in enabling gene delivery and overcoming tissue-penetration limitations in complex tumor environments. In this review, we provide a comprehensive oriented overview of optogenetics in oncology. We first analyze the molecular mechanisms and engineering principles of representative optogenetic tools, with a focus on LOV- and CRY2-based systems. We then highlight recent advances in biomaterial-assisted optogene delivery and light delivery strategies, emphasizing their material-dependent mechanisms that enable precise spatiotemporal control in vivo. Furthermore, we summarize emerging preclinical applications in cancer immunotherapy, gene regulation, and intracellular signaling control. Finally, we discuss key challenges in biosafety, kinetic optimization, and clinical scalability, and outline future directions that integrate optogenetics with functional materials and intelligent design to realize clinically viable platforms. This review aims to provide a framework for the development of clinically viable optogenetic platforms for next-generation cancer therapy.

Abstract: The cytoskeleton is a dynamic intracellular network that governs cell shape, migration, division, and mechanotransduction. Precise spatiotemporal control of cytoskeletal regulation is essential for understanding how these processes are coordinated in physiology and disease, yet conventional pharmacological and genetic approaches often lack sufficient resolution or reversibility. Optogenetic technologies provide a powerful alternative by enabling light-controlled, noninvasive manipulation of cytoskeletal regulators with high temporal precision and subcellular specificity. This review summarizes recent advances in genetically encoded optogenetic tools for interrogating cytoskeletal dynamics. We discuss core design strategies, including allosteric regulation, light-induced oligomerization, heterodimerization, and dissociation, and highlight representative applications targeting actin filaments, microtubules, and upstream signaling pathways such as Rho family GTPases. We conclude by outlining current limitations and emerging directions, including improved tissue penetration, reduced phototoxicity, and multiplexed optical control, which are expected to further expand the utility of optogenetics in cytoskeleton research.

Abstract: Light is a pivotal environmental signal regulating diverse plant developmental and physiological processes, including seed germination, hypocotyl elongation, phototropism, metabolite biosynthesis, stress resistance, temperature response, and circadian rhythms. Multiple signal transduction pathways of ultraviolet, blue light, and red/far-red light as well as related protein interaction networks in plants have been identified. Deciphering the mechanisms of light perception and signal transduction is of great significance to crop breeding and optogenetic manipulation. Structural biology has profoundly advanced the studies of light signal transduction by elucidating high-resolution three-dimensional (3D) structures of photoreceptors and their downstream signaling components. These studies uncover the molecular basis underlying perception and transduction of different light signals by plants. This review summarizes key structural findings of plant light signal transduction, highlighting the architectures and molecular functions of photoreceptors and associated signaling factors. We also outline the mechanisms underlying photoreceptor activation, inhibition, and regulatory interactions within light signaling networks and discuss the challenges in this field.

Abstract: Light-induced membrane fusion has become a pivotal technique for constructing and functionalizing synthetic cells by enabling precise control over membrane merging events. Traditional fusion approaches that rely on chemical, physical, and mechanical stimuli frequently lack both specificity and reversibility, limiting their utility in mimicking dynamic cellular processes. Here, we review advances employing photosensitive molecules and optogenetic tools that facilitate spatiotemporally controlled fusion of lipid and polymer vesicles, enabling dynamic content exchange and membrane remodeling. These approaches have enhanced synthetic cell assembly, molecular transport, and signal transduction, with applications extending to drug delivery and biosensing. Despite challenges in efficiency and biocompatibility, ongoing innovations in photosensitizer design and light activation strategies promise to expand the capabilities of synthetic biology platforms. This work underscores the potential of light-induced fusion to advance the development of intelligent nanomaterials and functional synthetic cellular systems.

Abstract: The light-mediated, specific, and precise control of cell functions enabled by optogenetics has become a versatile method for investigating and combatting cancer. An increasing set of optogenetic tools enables tightly controlled regulation of ion flux across biological membranes, gene expression, gene editing, and protein-protein interactions and is being used to interrogate hallmark traits of cancer at the cellular, subcellular, and organismic level. This enables, on the one hand, the identification of critical signaling circuits required for cancer development and progression in vitro and in animal models and can flag potential intervention points for pharmacologic interference. On the other hand, optogenetics can improve the level of control in cell-based therapeutics. The current article provides a review of optogenetic tools and approaches used in the cancer research field and their multiple applications for improving our understanding of signal transduction pathways, modulating immune functions in the tumor microenvironment, facilitating drug screening, or directly attacking cancer cells. Key advantages and achievements of optogenetics in the cancer research field and remaining barriers for clinical applications are discussed.

Abstract: Mitochondrial quality control is tightly associated with aging-related neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Previous studies reported that ALS/FTD-associated protein p62 drives "mitochondrial clustering" (perinuclear clustering of fragmented and swollen mitochondria) during PINK1/Parkin-mediated mitophagy, but the underlying molecular mechanism, especially the precise role of p62 in mitochondrial clustering during mitophagy and the potential relationship between the mitochondrial quality control mediated by p62 and disease pathogenesis of ALS/FTD, remains unclear. Here, using cell biology in combination with an optogenetic tool, we show that the phase separation (condensation) of p62 mediates the clustering of damaged mitochondria to form "grape-like" clusters during PINK1/Parkin-mediated mitophagy, which is tightly associated with aging-related neurodegenerative diseases. In addition, our data suggest this mitochondrial clustering process is an arrest mechanism driven by p62 condensation (beyond the function of other autophagy receptors in mitophagy), which acts as a "brake" to reduce the surface area of dysfunctional mitochondria within cytoplasm for minimizing mitochondrial turnover in cells. Moreover, ALS/FTD-related pathological mutations perturb p62 condensation, thereby inhibiting mitochondrial clustering and destroying the "brake" machinery of mitochondrial quality control. Together, our data highlight how p62 condensation modulates organelle quality control in cell biology, and the important role of p62 condensation in both physiology and pathology.

Abstract: Inducible translocation to subcellular compartments is a common strategy for protein switches that control a variety of cell behaviors. However, existing switches achieve translocation through induced dimerization, requiring constitutive anchoring of one component into the target compartment and optimization of relative expression levels between the two components. We present a simpler, single-component strategy called Avidity-assisted targeting (Aviatar). Aviatar achieves translocation with only a single protein by converting low-affinity monomers into high-avidity assemblies through inducible clustering. We demonstrated the Aviatar concept and its generality using optogenetic clustering to drive translocation to the plasma membrane, endosomes, golgi, endoplasmic reticulum, and microtubules using binding domains for lipids or endogenous proteins that were specific to those compartments. Aviatar recruitment regulated actin polymerization at the cell periphery and revealed compartment-specific signaling of receptor tyrosine kinase fusions associated with cancer. Finally, GFP-targeting Aviatar probes allowed inducible localization to any GFP-tagged target, including endogenously tagged stress granule proteins. Aviatar is a straightforward platform that can be rapidly adapted to a broad array of targets without the need for their prior modification or disruption.

Abstract: Cells process dynamic signaling inputs to regulate fate decisions during development. While oscillations or waves in key developmental pathways, such as Wnt, have been widely observed, the principles governing how cells decode these signals remain unclear. By leveraging optogenetic control of the Wnt signaling pathway in both HEK293T cells and H9 human embryonic stem cells, we systematically map the relationship between signal frequency and downstream pathway activation. We find that cells exhibit a minimal response to Wnt at certain frequencies, a behavior we term anti-resonance. We developed both detailed biochemical and simplified hidden variable models that explain how anti-resonance emerges from the interplay between fast and slow pathway dynamics. Remarkably, we find that frequency directly influences cell fate decisions involved in human gastrulation; signals delivered at anti-resonant frequencies result in dramatically reduced mesoderm differentiation. Our work reveals a previously unknown mechanism of how cells decode dynamic signals and how anti-resonance may filter against spurious activation. These findings establish new insights into how cells decode dynamic signals with implications for tissue engineering, regenerative medicine, and cancer biology.

Abstract: Biopolymers that separate into condensed and dilute phases in solution also prewet membranes when one or more components couple to membrane lipids. Here we demonstrate that this prewetting transition becomes exquisitely sensitive to lipid composition when membranes have compositions near the boundary of liquid-ordered/liquid-disordered phase coexistence in both simulation and in reconstitution when polyelectrolytes are coupled to model membranes. In cells, we use an optogenetic tool to characterize prewetting at both the plasma membrane (PM) and the endoplasmic reticulum (ER) and find that prewetting is potentiated or inhibited by perturbations of membrane composition. Prewetting can also mediate membrane adhesion, with avidity dependent on membrane composition, as demonstrated in cells through the potentiation or inhibition of ER-PM contact sites. The strong correspondence of results in simulation, reconstitution and cells reveals a new role for membrane lipids in regulating the recruitment and assembly of soluble proteins.

Abstract: Precise regulation of protein abundance is essential for understanding dynamic cellular processes and for advancing therapeutic development. However, existing approaches lack the spatiotemporal resolution required to these cellular processes. Recent advances in optogenetics have enabled the design of optogenetic targeted protein degradation systems (Opto-TPD) allowing reversible and non-invasive control of protein stability with high spatiotemporal precision. In this review, we systematically summarize the design principles of Opto-TPD tools, including those based on light-oxygen-voltage (LOV)-domain conformational systems, light-inducible dimerization systems, and light-controlled degradation tool expression systems. We further highlight their applications in probing protein function, modulating signaling pathways, and therapeutic translations. By comparing the mechanistic features, performance, and limitations of each platform, we aim to provide a comprehensive resource for guiding future tool optimization. Altogether, these Opto-TPD tools represent a powerful and versatile complement to existing protein manipulation technologies, expanding the toolbox for precise control of protein homeostasis in living systems.

Abstract: When mammalian cells are exposed to stress, they co-ordinate the condensation of stress granules (SGs) through the action of proteins G3BP1 and G3BP2 (G3BPs) and, simultaneously, undergo a massive reduction in translation. Although SGs and G3BPs have been linked to this translation response, their overall impact has been unclear. Here we investigate the question of how, and indeed whether, G3BPs and SGs shape the stress translation response. We find that SGs are enriched for mRNAs that are resistant to the stress-induced translation shutdown. Although the accurate recruitment of these stress-resistant mRNAs does require the context of stress, a combination of optogenetic tools and spike-normalized ribosome profiling demonstrates that G3BPs and SGs are necessary and sufficient to both help prioritize the translation of their enriched mRNAs and help suppress cytosolic translation. Together, these results support a model in which G3BPs and SGs reinforce the stress translation programme by prioritizing the translation of their resident mRNAs.

Abstract: Cellular receptors serve as central hubs that translate external signals into intracellular programs governing cell fate, function and behavior. Achieving precise and reversible control over receptor activity has long been a major challenge in both fundamental biology and translational medicine. Optogenetic receptor engineering provides a transformative solution by integrating photosensitive domains into natural receptor frameworks. This strategy enables light-dependent modulation of signaling with high spatial and temporal precision while maintaining minimal disturbance to endogenous pathways. Unlike chemogenetic systems or classical photoreceptive ion channels, this approach preserves endogenous ligand specificity and avoids slow ligand diffusion/clearance-associated artifacts. Through such systems, researchers can dissect causal relationships in dynamic signaling events, finely manipulate neuromodulatory and immune circuits and program cellular activities involved in development and tissue regeneration. The approach also allows quantitative control of signaling intensity and duration, offering new opportunities for linking molecular design to physiological outcomes. By combining optogenetic principles with advances in materials science and bioelectronics, future designs may achieve improved optical fidelity, enhanced light penetration and better signal amplification within complex biological environments. Integration with AI-guided protein engineering may also accelerate the discovery of optimized photosensory-receptor pairings. Together, these developments point to an emerging field where light-responsive receptors function as programmable interfaces between photonic control and cellular computation. In summary, the engineering of optogenetic receptors establishes a conceptual and technological framework for reversible, accurate and tunable regulation of cellular communication. This review summarizes current progress, outlines key design principles and provides conceptual guidelines for advancing next-generation light-responsive receptors and their biomedical applications. However, key translational challenges-including immunogenicity of non-human photoreceptors, limited gene-delivery efficiency and long-term biosafety-remain to be addressed through nonviral delivery strategies, autologous cell engineering and de-immunized or humanized photoreceptor design.

Abstract: Multimerization and phase separation represent two paradigms for organizing receptor tyrosine kinases (RTKs). However, their functional distinctions from the perspective of biomolecular organization remain unclear. Here, we present CORdensate, a light-controllable condensation system combining two synergistic photoactuators: oligomeric Cry2 and heterodimeric LOVpep/ePDZ. Engineering single-chain photoswitches, we achieve four biomolecular organization patterns ranging from monomerization to phase separation. CORdensate exhibits constant assembly and disassembly kinetics. Applying CORdensate to mimic pathogenic RTK granules establishes the role of phase separation in activating ALK and RET. Moreover, assembling ALK and RET through varying organization patterns, we highlight the superior organizational ability of phase separation over multimerization. Additionally, CORdensate-based RTK granules suggest that phase separation broadly and robustly activates RTKs. This study introduces a optogenetic tool for investigating biomolecular condensation.

Abstract: The modification of key enzymes for chemical production plays a crucial role in enhancing the yield of targeted products. However, manipulating key nodes in specific signalling pathways remains constrained by traditional gene overexpression or knockout strategies. Discovering and designing optogenetic tools enable us to regulate enzymatic activity or gene expression at key nodes in a spatiotemporal manner, rather than relying solely on chemical induction throughout production processes. In this review, we discuss the recent applications of optogenetic tools in the regulation of microbial metabolites, plant sciences and disease therapies. We categorize optogenetic tools into five classes based on their distinct applications. First, light-induced gene expression schedules can balance the trade-off between chemical production and cell growth phases. Second, light-triggered liquid-liquid phase separation (LLPS) modules provide opportunities to co-localize and condense key enzymes for enhancing catalytic efficiency. Third, light-induced subcellular localized photoreceptors enable the relocation of protein of interest across various subcellular compartments, allowing for the investigation of their dynamic regulatory processes. Fourth, light-regulated enzymes can dynamically regulate production of cyclic nucleotides or investigate endogenous components similar with conditional depletion or recovery function of protein of interest. Fifth, light-gated ion channels and pumps can be utilized to investigate dynamic ion signalling cascades in both animals and plants, or to boost ATP accumulation for enhancing biomass or bioproduct yields in microorganisms. Overall, this review aims to provide a comprehensive overview of optogenetic strategies that have the potential to advance both basic research and bioindustry within the field of synthetic biology.

Abstract: Protein homeostasis, or proteostasis, is essential for cellular proteins to function properly. The buildup of abnormal proteins (such as damaged, misfolded, or aggregated proteins) is associated with many diseases, including cancer. Therefore, maintaining proteostasis is critical for cellular health. Currently, genetic methods for modulating proteostasis, such as RNA interference and CRISPR knockout, lack spatial and temporal precision. They are also not suitable for depleting already-synthesized proteins. Similarly, molecular tools like PROTACs and molecular glue face challenges in drug design and discovery. To directly control targeted protein degradation within cells, we introduce an intrabody-based optogenetic toolbox named Flash-Away. Flash-Away integrates the light-responsive ubiquitination activity of the RING domain of TRIM21 for protein degradation, coupled with specific intrabodies for precise targeting. Upon exposure to blue light, Flash-Away enables rapid and targeted degradation of selected proteins. This versatility is demonstrated through successful application to diverse protein targets, including actin, MLKL, and ALFA-tag fused proteins. This innovative light-inducible protein degradation system offers a powerful approach to investigate the functions of specific proteins within physiological contexts. Moreover, Flash-Away presents potential opportunities for clinical translational research and precise medical interventions, advancing the prospects of precision medicine.

Abstract: Intracellular optogenetics represents a rapidly advancing biotechnology that enables precise, reversible control of protein activity, signaling dynamics, and cellular behaviours using genetically encoded, light-responsive systems. Originally pioneered in neuroscience through channelrhodopsins to manipulate neuronal excitability, the field has since expanded into diverse intracellular applications with broad implications for medicine, agriculture, and biomanufacturing. Key to these advances are photoreceptors such as cryptochrome 2 (CRY2), light-oxygen-voltage (LOV) domains, and phytochromes, which undergo conformational changes upon illumination to trigger conditional protein-protein interactions, localization shifts, or phase transitions. Recent engineering breakthroughs-including the creation of red-light responsive systems such as MagRed that exploit endogenous biliverdin-have enhanced tissue penetration, minimized phototoxicity, and expanded applicability to complex biological systems. This review provides an overarching synthesis of the molecular principles underlying intracellular optogenetic actuators, including the photophysical basis of light-induced conformational changes, oligomerization, and signaling control. We highlight strategies that employ domain fusions, rational mutagenesis, and synthetic circuits to extend their utility across biological and industrial contexts. We also critically assess current limitations, such as chromophore dependence, light delivery challenges, and safety considerations, so as to frame realistic paths towards translation. Looking ahead, future opportunities include multi-colour and multiplexed systems, integration with high-throughput omics and artificial intelligence, and development of non-invasive modalities suited for in vivo and industrial applications. Intracellular optogenetics is thus emerging as a versatile platform technology, with the potential to reshape how we interrogate biology and engineer cells for therapeutic, agricultural, and environmental solutions.

Abstract: Cancer can result from abnormal regulation of cells by their environment, potentially because cancer cells may misperceive environmental cues. However, the magnitude to which the oncogenic state alters cellular information processing has not been quantified. Here, we apply pseudorandom pulsatile optogenetic stimulation, live-cell imaging, and information theory to compare the information capacity of receptor tyrosine kinase (RTK) signaling pathways in EML4-ALK-driven lung cancer (STE-1) and in non-transformed (BEAS-2B) cells. The average information rate through RTK/ERK signaling in STE-1 cells was less than 0.5 bit/hour, compared to 7 bit/hour in BEAS-2B cells, but increased to 3 bit/hour after oncogene inhibition. Information was transmitted by 50-70% of cells, whose channel capacity (maximum information rate) was estimated through in silico protocol optimization. In BEAS-2B cells, channel capacity of the parallel RTK/calcineurin pathway surpassed that of the RTK/ERK pathway. This study highlights information capacity as a sensitive metric for identifying disease-associated dysfunction and evaluating the effects of targeted interventions.

Abstract: Cells constantly encounter environmental and physiological fluctuations that challenge homeostasis and threaten viability. In response to these cues, specific proteins and nucleic acids engage in multivalent interactions and undergo phase separation to form membraneless assemblies known as biomolecular condensates. Nuclear condensates include paraspeckles, nuclear speckles, and Cajal bodies, while cytoplasmic condensates include stress granules, processing bodies, RNA transport granules, U-bodies, and Balbiani bodies. These assemblies regulate transcription, splicing fidelity, RNA stability, translational reprogramming, and integration of signaling pathways, thereby serving as dynamic platforms for metabolic regulation and physiological adaptation. However, dysregulation of these condensates has been increasingly recognized as a central pathogenic mechanism in neurodegenerative diseases, cancers, and viral infections, contributing to toxic protein aggregation, nucleic acid dysregulation, and aberrant cell survival signaling. This review provides a comprehensive synthesis of the molecular mechanisms governing condensation, delineates the diverse types and functions of major biomolecular condensates, and examines therapeutic approaches based on their pathophysiological relevance to disease development and progression. Furthermore, we highlight the cutting-edge technologies, including CRISPR/Cas-based imaging, optogenetic manipulation, and AI-driven phase separation prediction tools, which enable the real-time monitoring and precision targeting of cytoplasmic biomolecular condensates. These insights underscore the emerging potential of biomolecular condensates as both biomarkers and therapeutic targets, paving the way for precision medicine approaches in condensate-associated diseases.

Abstract: Human topoisomerase IIβ binding protein 1 (TopBP1) is a scaffold protein involved in DNA replication initiation, DNA repair, transcription regulation, and checkpoint activation. TopBP1 forms nuclear condensates that act as a molecular switch to amplify ATR activity and promote the activation of the checkpoint effector kinase Chk1. In cancer cells, ATR activity is crucial to tolerate the intrinsically high level of DNA lesions and obstacles that block replication fork progression. Thus, ATR inhibitors are currently tested in clinical trials, often in combination with chemotherapy drugs. However, resistance and toxicity are still major issues. The weak interactions that hold TopBP1 condensates together are highly sensitive to changes in the cellular milieu, suggesting that small molecules may alter the formation of TopBP1 condensates. Here, we developed a high-throughput screening system to identify TopBP1 condensation modulators. This system allowed us to identify FDA-approved drugs, including thimerosal and quinacrine, that inhibit TopBP1 condensation and block the activation of ATR/Chk1 signaling. Mechanistically, quinacrine impaired TopBP1's ability to associate with chromatin, thereby interfering with its capacity to form condensates. Furthermore, quinacrine enhanced the therapeutic efficacy of 5-fluorouracil and irinotecan, components of the clinically used FOLFIRI regimen in a mouse model of peritoneal carcinomatosis from colorectal cancer.

Abstract: Microtubules (MTs) form dynamic cytoskeletal scaffolds essential for intracellular transport, organelle positioning, and spatial organization of signaling. Their architecture and function are continuously remodeled through the concerted actions of microtubule-associated proteins (MAPs), post-translational modifications (PTMs), and molecular motors. To precisely interrogate these processes in living systems, we developed a genetically encoded optogenetic toolkit for spatiotemporal control of MT organization and dynamics. By replacing native multimerization motifs with a blue light-responsive oligoermization domain, we have engineered single-component probes, OptoMT and OptoTIP, that reversibly label MT polymers or track plus-ends with tunable kinetics from seconds to minutes. When coupled to enzymatic effectors, these modules enable localized tubulin acetylation or detyrosination, directly linking PTMs to MT stability. We further engineered OptoMotor, a light-activatable kinesin platform that reconstitutes tail-dependent cargo transport along MTs, and OptoSAW, a light-triggered severing actuator for controlled MT disassembly. Using these tools, we reveal how local MT integrity governs lysosomal trafficking and ER-associated signaling dynamics. Collectively, this versatile single-component toolkit bridges molecular design with cytoskeletal function, offering new avenues to illuminate how dynamic cytoskeletal architectures coordinate intracellular organization, transport, and signaling.

Abstract: Mitochondrial membrane potential (MMP) is essential for mitochondrial functions, yet current methods for modulating MMP lack precise spatial and temporal control. Here, we present an optogenetic system that enables reversible formation of inter-mitochondrial contacts (mito-contacts) with high spatiotemporal precision. Blue light stimulation induces rapid formation of mito-contacts, which fully dissipate upon cessation of illumination. These light-induced mito-contacts can enhance MMP, leading to increased ATP production under stress conditions. Moreover, in human retinal cells and C. elegans, high MMP induced by mito-contacts alleviates the deleterious effects of prolonged blue light exposure, restoring energy metabolism and extending organismal lifespan. This optogenetic approach provides a powerful tool for modulating MMP and offers potential therapeutic applications for diseases linked to mitochondrial dysfunction.

Abstract: Oligomerization of photoactivatable proteins underlies many optogenetic strategies, yet their assembly states remain difficult to quantify in living cells. Here, we applied photon counting histogram analysis to directly measure the oligomerization of widely used optogenetic modules, Vaucheria frigida Aureochrome light-oxygen-voltage (VfAuLOV) and Arabidopsis thaliana cryptochrome 2 (AtCRY2), in living HEK293T cells. Oligomerization of both photoactivatable protein variants is concentration-dependent in cells. VfAuLOV primarily forms dimers, whereas AtCRY2 transitions into tetramers at concentrations above 1,000 nM, consistent with cryoEM structures. Human CRY2 exhibits light-independent oligomerization, while inactive AtCRY2 mutants (D387A and R439L) remain monomeric in light or darkness. Surprisingly, the constitutively active AtCRY2(W374) mutant still undergoes light-mediated oligomerization. The extent of light-induced lytic cell death correlates with the oligomerization state of these proteins when fused to receptor-interacting serine/threonine protein kinase 3. This study establishes a quantitative framework to resolve protein assembly dynamics in living cells, advancing mechanistic understanding of optogenetic tools and broadening their applications in cell signaling research.

Abstract: Since its discovery, the cyclic GMP-AMP synthase (cGAS)-stimulator of the interferon gene (STING) signaling pathway has been considered a pivotal component of innate immunity and a promising target for cancer immunotherapy. Beyond its canonical role in pathogen defense, accumulating evidence has demonstrated that the cGAS-STING pathway critically regulates diverse cellular processes, including cellular senescence, autophagy, cell death, and tumor immunosurveillance; therefore, dysregulation of this pathway correlates with the pathogenesis and progression of various human diseases, ranging from autoimmune and inflammatory disorders to cancer. Herein, we reviewed the regulatory mechanisms and cellular functions of the cGAS-STING pathway, highlighting its essential role in maintaining immune homeostasis. We systematically discussed the dual roles of the cGAS-STING pathway in cancer immunity, in which it triggers both antitumor and immunosuppressive effects. Finally, we summarized the recent advances and challenges in therapeutic strategies targeting the cGAS-STING pathway and discussed the next generation of therapies, including nanomaterials, antibody-drug conjugates, engineered bacteria, alternative strategies, optogenetic approaches, and combination strategies. We hope that our efforts will advance the understanding of the fundamental principles of innate immune recognition and response, and provide novel directions for improving the clinical outcomes of cGAS-STING-targeted therapies.

Abstract: Optogenetics, a modern tool to control cellular excitability in a non-invasive way, has widely been used in neuroscience. Recently, optogenetic approaches begin to be applied to studies of other biological phenomena including muscle functions. For these analyses, chicken embryos serve as an excellent model animal since they are highly amenable to site-specific manipulations with genes of optogenetics such as Channelrhodopsins, and its following targeted light irradiation. We here overview recent progresses in optogenetics using chicken embryos with a highlight on the studies of axon pathfinding, gut peristalsis, and feather morphogenesis.

Abstract: Cellular immunotherapy has transformed cancer treatment by harnessing T cells to target malignant cells. However, its broader adoption is hindered by challenges such as efficacy loss, limited persistence, tumor heterogeneity, an immunosuppressive tumor microenvironment (TME), and safety concerns related to systemic adverse effects. Optogenetics, a technology that uses light-sensitive proteins to regulate cellular functions with high spatial and temporal accuracy, offers a potential solution to overcome these issues. By enabling targeted modulation of T cell receptor signaling, ion channels, transcriptional programming, and antigen recognition, optogenetics provides dynamic control over T cell activation, cytokine production, and cytotoxic responses. Moreover, optogenetic strategies can be applied to remodel the TME by selectively activating immune responses or inducing targeted immune cell depletion, thereby enhancing T cell infiltration and immune surveillance. However, practical hurdles such as limited tissue penetration of visible light and the need for cell- or tissue-specific gene delivery must be addressed for clinical translation. Emerging solutions, including upconversion nanoparticles, are being explored to improve light delivery to deeper tissues. Future integration of optogenetics with existing immunotherapies, such as checkpoint blockade and adoptive T cell therapies, could improve treatment specificity, minimize adverse effects, and provide real-time control over immune responses. By refining the precision and adaptability of immunotherapy, optogenetics promises to further enhance both the safety and efficacy of cancer immunotherapy.