Curated Optogenetic Publication Database

Abstract: Inducible expression of endogenous and foreign genes has been a pivotal driving force behind a lot many seminal breakthroughs in biotechnology. Synthetic biology, a very promising field, largely relies on transgene expression platforms which facilitate convenient and conditional regulation. Optogenetic approaches that exploit light to steer biological events, e.g., gene expression, with excellent spatiotemporal control, are often more precise compared to chemical induction. Light being an omnipresent environmental stimulus, serves as the ideal cue, and enables high spatiotemporal accuracy with respect to gene expression. In this review, we focus on different elements relevant to light-inducible gene expression - light-responsive promoters, light-regulated transcription factors, and photocaged inducers. Using light as a binary input function, we explore the essence of logic gates towards the development of gene expression circuits - thereby understanding the entanglement between optogenetics and synthetic biology. We primarily focus on prokaryotes, but also draw comparisons with analogous eukaryotic gene expression systems.

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: 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: Light exerts a profound influence on plant growth and development, functioning both as a primary energy source and as a critical environmental signal. Red light (RL) and blue light (BL) are the principal spectral regions driving photosynthesis, and consequently promoting autotrophic growth. Compared with RL and BL, green light (GL) has long been considered an inefficient component of the photosynthetically active radiation spectrum in terrestrial plants and has been reported to play a contradictory role in plant development. This review aims to provide a comprehensive understanding of GL's implications for plant developmental processes. Considering that the lack of a specific GL receptor has frustrated the utilization of GL, we discussed the possible photoreceptors that may mediate GL responses in terrestrial plants. Furthermore, we highlight the promising applications of GL-based optogenetics strategies for smart agricultural systems.

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: Microtubules are crucial regulators of plant development and are organized by a suite of microtubule-associated proteins (MAPs) that can rapidly remodel the array in response to various cues. This complexity has inspired countless studies into microtubule function from the subcellular to tissue scale, revealing an ever-increasing number of microtubule-dependent processes. Developing a comprehensive understanding of how local microtubule configuration, dynamicity, and remodeling drive developmental progression requires new approaches to capture and alter microtubule behavior. In this review, we will introduce the technological advancements we believe are poised to transform the study of microtubules in plant cells. In particular, we focus on (1) advanced imaging and analysis methods to quantify microtubule organization and behavior, and (2) novel tools to target specific microtubule populations in vivo. By showcasing innovative methodologies developed in non-plant systems, we hope to motivate their increased adoption and raise awareness of possible means of adapting them for studying microtubules in plants.

Abstract: Cellular signaling cascades rely on transfer of information from one protein to another or within a single protein. To facilitate signal integration, specific structural motifs evolved that allow signal processing and also enable modular downstream response integration, facilitating sophisticated regulatory mechanisms. On a structural level, especially coiled-coil helices are frequently observed as signaling motifs. In diguanylate cyclases (DGCs) featuring GGDEF domains, N-terminal coiled-coils frequently activate systems by rearrangements of the interdimer active site. The variety of sensory domains that modulate this structural equilibrium in response to different stimuli highlights the importance of DGCs in bacterial adaptation. One interesting example of sensor DGCs is blue light-activated light-oxygen-voltage (LOV)-GGDEF couples. Here, we describe molecular details of a two-stage mechanism that allows tight dark-state inhibition while enabling high enzymatic activities upon illumination, achieving fold changes exceeding 10,000-fold. Using an in vivo activity assay, we screened amino acid substitutions at the inhibitory interface and the sensor-effector linker region to identify variants that promote enzymatic activity in the dark. In combination with chimeras of LOV and GGDEF domains preventing inhibitory interface formation, we successfully stabilized elongated active-state conformations and confirmed the role of the inhibitory interface between sensor and effector in the tight dark-state inhibition. Interestingly, the initially generated chimeras are still light regulatable as long as the linker sequence is not stabilized in either inhibiting or stimulating coiled-coil register. Our results offer valuable insights for potential optogenetic applications but also demonstrate inherent challenges associated with Methylotenera sp. LOV-activated DGCs.

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: 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: T-cell activation is a highly regulated process requiring both antigen recognition via the T-cell receptor (TCR) and co-stimulatory signaling, notably through the co-stimulatory receptor CD28. Here, we introduce an optogenetic platform for reversible and tunable full activation of human T cells that does not require genetic modification. We engineered opto-CD28-REACT, a recombinant protein comprising an anti-CD28 single-chain variable fragment, GFP, and phytochrome-interacting factor 6 (PIF6). This construct binds CD28 and thereby attaches PIF6 to CD28. Upon red light (630 nm) illumination, PIF6 binds to PhyB tetramer-coated beads, triggering CD28 signaling that can be attenuated by far-red light (780 nm) in 2 min. We show that opto-CD28-REACT synergizes with opto-CD3ϵ-REACT-a complementary optogenetic tool targeting the TCR complex-to induce light-dependent activation of both Jurkat cells and primary human T cells. Co-stimulation through both opto-REACT systems promotes ERK phosphorylation, upregulation of the activation markers CD69 and CD25, interleukin-2 (IL-2) secretion, and T-cell proliferation, reaching levels similar to conventional antibody-mediated stimulation. This strategy enables precise optical control over TCR and CD28 signaling in non-genetically modified T cells, offering a powerful approach for dissecting the regulatory dynamics of T-cell activation and advancing applications in synthetic immunology.

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.

Abstract: Over the past two decades, optogenetics has evolved from a conceptual framework into a powerful and versatile technology for controlling cellular processes with light. Rooted in the discovery and characterization of natural photoreceptors, the field has advanced through the development of genetically encoded, light-sensitive proteins that enable precise spatiotemporal control of ion flux, intracellular signaling, gene expression, and protein interactions. This review traces key milestones in the emergence of optogenetics and highlights the development of major optogenetic tools. From the perspective of genetic tool innovation, the focus is on how these tools have been engineered and optimized for novel or enhanced functions, altered spectral properties, improved light sensitivity, subcellular targeting, and beyond. Their broadening applications are also explored across neuroscience, cardiovascular biology, hematology, plant sciences, and other emerging fields. In addition, current trends such as all-optical approaches, multiplexed control, and clinical translation, particularly in vision restoration are discussed. Finally, ongoing challenges are addressed and outline future directions in optogenetic tool development and in vivo applications, positioning optogenetics as a transformative platform for basic research and therapeutic advancement.

Abstract: Oncolytic virus (OVs) therapy has emerged as a promising modality in cancer immunotherapy, attracting growing attention for its multifaceted mechanisms of tumor elimination. However, its efficacy as a monotherapy remains constrained by physiological barriers, limited delivery routes, and suboptimal immune activation. Phototherapy, an innovative and rapidly advancing cancer treatment technology, can mitigate these limitations when used in conjunction with OVs, enhancing viral delivery, amplifying tumor destruction, and boosting antitumor immune responses. This review provides the first comprehensive analysis of synergistic integration of OVs with both photodynamic therapy (PDT) and photothermal therapy (PTT). It also explores their applications in optical imaging-guided diagnosis and optogenetically controlled delivery. Furthermore, it discusses emerging strategies involving biomimetic virus or viroid-based vectors in conjunction with phototherapy, and delves into the immunomodulatory mechanisms of this combinatorial approach. While promising in preclinical models, these combined strategies are still largely in early-stage research. Challenges such as limited light penetration, delivery efficiency, and safety concerns remain to be addressed for clinical translation. Consequently, the integration of OV therapy and phototherapy represents a compelling strategy in cancer treatment, offering significant promise for advancing precision oncology and next-generation immunotherapies.

Abstract: Clustered regularly interspaced short palindromic repeats (CRISPR) technology represents a landmark advance in the field of gene editing. However, conventional CRISPR/Cas systems are limited by inadequate temporal and spatial control. In recent years, the development of optically controlled CRISPR (Opto-CRISPR) technology has offered a novel solution to this issue. As a combination of optogenetics and the CRISPR technology, the Opto-CRISPR technology enables dynamic space-time-specific gene editing and regulation in cells and organisms. In this review, we concisely introduce the basic principles of Opto-CRISPR, summarize its operational mechanisms, and discuss its applications and recent advances across various research fields. In addition, this review analyzes the limitations of Opto-CRISPR, aiming to provide a reference for the development of this emerging field.

Abstract: Plant science has entered a transformative era as genome editing enables precise DNA modifications to address global challenges such as climate adaptation and food security. These modifications are primarily driven by the integration of three modular components-DNA-targeting modules, effector modules, and control modules-that can be selectively activated or suppressed. The field has evolved from protein-based systems (e.g., zinc finger nucleases and transcription activator-like effector nucleases) to RNA-guided systems (e.g., CRISPR-Cas) that can control both genetic and epigenetic states. Modular pairing of DNA-targeting and effector domains, with or without inducible control, enables precise transcriptional regulation and chromatin remodeling. The present review examines these three modules and highlights strategies for their optimization. It also outlines innovative tools, such as optogenetic and receptor-integrated systems, that enable spatiotemporal control over genome editor expression. These modular approaches bypass traditional limitations and allow scientists to create plants with desirable traits, decipher complex gene networks, and promote sustainable agriculture.

Abstract: Light is a critical environmental factor that governs the growth and development of plants. Plants have specialised photoreceptor proteins, which allow them to sense both quality and quantity of light and drive a wide range of responses critical for optimising growth, resource use and adaptation to changes in environment. Understanding the role of these photoreceptors in plant biology has opened up potential avenues for engineering crops with enhanced productivity by engineering photoreceptor activity and/or action. The ability to manipulate plant genomes through genetic engineering and synthetic biology approaches offers the potential to unlock new agricultural innovations by fine-tuning photoreceptors or photoreceptor pathways that control plant traits of agronomic significance. Additionally, optogenetic tools which allow for precise, light-triggered control of plant responses are emerging as powerful technologies for real-time manipulation of plant cellular responses. As these technologies continue to develop, the integration of photoreceptor engineering and optogenetics into crop breeding programs could potentially revolutionise how plant researchers tackle challenges of plant productivity. Here we provide an overview on the roles of key photoreceptors in regulating agronomically important traits, the current state of plant photoreceptor engineering, the emerging use of optogenetics and synthetic biology, and the practical considerations of applying these approaches to crop improvement. This review seeks to highlight both opportunities and challenges in harnessing photoreceptor engineering approaches for enhancing plant productivity. In this review, we provide an overview on the roles of key photoreceptors in regulating agronomically important traits, the current state of plant photoreceptor engineering, the emerging use of optogenetics and synthetic biology, and the practical considerations of applying these approaches to crop improvement.

Abstract: Bacterial therapy has emerged as a promising approach for disease treatment due to its environmental sensitivity, immunogenicity, and modifiability. However, the clinical application of engineered bacteria is limited by differences of expression levels in patients and possible off-targeting. Optogenetics, which combines optics and genetics, offers key advantages such as remote controllability, non-invasiveness, and precise spatiotemporal control. By utilizing optogenetic tools, the behavior of engineered bacteria can be finely regulated, enabling on-demand control of the dosage and location of their therapeutic products. In this review, we highlight the latest advancements in the optogenetic engineering of bacteria for light-controlled disease theranostics and therapeutic regulation. By constructing a three-dimensional analytical framework of “sense-produce-apply”, we begin by discussing the key components of bacterial optogenetic systems, categorizing them based on their photosensitive protein response to blue, green, and red light. Next, we introduce innovative light-producing tools that extend beyond traditional light sources. Then, special emphasis is placed on the biomedical applications of optogenetically engineered bacteria in treating diseases such as cancer, intestinal inflammation and systemic disease regulation. Finally, we address the challenges and future prospects of bacterial optogenetics, outlining potential directions for enhancing the safety and efficacy of light-controlled bacterial therapies. This review aims to provide insights and strategies for researchers working to advance the application of optogenetically engineered bacteria in drug delivery, precision medicine and therapeutic regulation.

Abstract: Transcription factors relay information from the external environment to gene regulatory networks that control cell physiology. To confer signalling specificity, robustness and coordination, these signalling networks use temporal communication codes, such as the amplitude, duration or frequency of signals. Although much is known about how temporal information is encoded, a mechanistic understanding of how gene regulatory networks decode signalling dynamics is lacking. Recent advances in our understanding of phase separation of transcriptional condensates provide new biophysical frameworks for both temporal encoding and decoding mechanisms. In this Perspective, we summarize the mechanisms by which transcriptional condensates could enable temporal decoding through signal adaptation, memory and persistence. We further outline methods to probe and manipulate dynamic communication codes of transcription factors and condensates to rationally control gene activation.

Abstract: Adrenoceptors (ARs) play a vital role in various physiological processes and are key therapeutic targets. The advent of optical control techniques, including optogenetics and photopharmacology, offers the potential to modulate AR signaling with precise temporal and spatial resolution. In this review, we summarize the latest advancements in the optical control of AR signaling, encompassing optogenetics, photocaged compounds, and photoswitchable compounds. We also discuss the limitations of current tools and provide an outlook on the next generation of optogenetic and photopharmacological tools. These emerging optical technologies not only enhance our understanding of AR signaling but also pave the way for potential therapeutic developments.

Abstract: Optogenetics has substantially enhanced our understanding of biological processes by enabling high-precision tracking and manipulation of individual cells. It relies on photosensitive proteins to monitor and control cellular activities, thereby paving the way for significant advancements in complex system research. Photosensitive proteins play a vital role in the development of optogenetics, facilitating the establishment of cutting-edge methods. Recent breakthroughs in protein design have opened up opportunities to develop protein-based tools that can precisely manipulate and monitor cellular activities. These advancements will significantly accelerate the development and application of optogenetic tools. This article emphasizes the pivotal role of protein design in the development of optogenetic tools, offering insights into potential future directions. We begin by providing an introduction to the historical development and fundamental principles of optogenetics, followed by an exploration of the operational mechanisms of key photosensitive domains, which includes clarifying the conformational changes they undergo in response to light, such as allosteric modulation and dimerization processes. Building on this foundation, we reveal the development of protein design tools that will enable the creation of even more sophisticated optogenetic techniques.

Abstract: Optogenetics is an empowering technology that uses light-responsive proteins to control biological processes. Because of its genetic tractability, abundance of genetic tools, and robust culturing conditions, Saccharomyces cerevisiae has served for many years as an ideal platform in which to study, develop, and apply a wide range of optogenetic systems. In many instances, yeast has been used as a steppingstone in which to characterize and optimize optogenetic tools to later be deployed in higher eukaryotes. More recently, however, optogenetic tools have been developed and deployed in yeast specifically for biotechnological applications, including in nonconventional yeasts. In this review, we summarize various optogenetic systems responding to different wavelengths of light that have been demonstrated in diverse yeast species. We then describe various applications of these optogenetic tools in yeast, particularly in metabolic engineering and recombinant protein production. Finally, we discuss emerging applications in yeast cybergenetics-the interfacing of yeast and computers for closed-loop controls of yeast bioprocesses-and the potential impact of optogenetics in other future biotechnological applications.

Abstract: The model liverwort Marchantia polymorpha is an emerging testbed species for plant metabolic engineering but lacks well-characterized inducible promoters, which are necessary to minimize biochemical and physiological disruption when over-accumulating target products. Here, we demonstrate the functionality of the light-inducible plant-usable light-switch elements (PULSE) optogenetic system in Marchantia and exemplify its use through the light-inducible overproduction of the bioplastic poly-3-hydroxybutyrate (PHB).

Abstract: Immunotherapy, the medicinal modulation of a host's immune response to better combat a pathogen or disease, has transformed cancer treatments in recent decades. T-cells, an important component of the adaptive immune system, are further paramount for therapy success. Recent immunotherapeutic modalities have therefore more frequently targeted T-cells for cancer treatments and other pathologies and are termed adoptive T-cell (ATC) therapies. ATC therapies characterize various types of immunotherapies but predominantly fall into three established techniques: tumour-infiltrating lymphocyte, chimeric antigen receptor T-cell, and engineered T-cell receptor therapies. Despite promising clinical results, all ATC therapy types fall short in providing long-term sustained tumour clearance while being particularly ineffective against solid tumours, with substantial developments aiming to understand and prevent the typical drawbacks of ATC therapy. Optogenetics is a relatively recent development, incorporating light-sensitive protein domains into cells or tissues of interest to optically tune specific biological processes. Optogenetic manipulation of immunological functions is rapidly becoming an investigative tool in immunology, with light-sensitive systems now being used to optimize many cellular therapeutic modalities and ATC therapies. This review focuses on how optogenetic approaches are currently utilized to improve ATC therapy in clinical settings by deepening our understanding of the molecular rationale behind therapy success. Moreover, this review further critiques current immuno-optogenetic systems and speculates on the expansion of recent developments, enhancing current ATC-based therapeutic modalities to pave the way for clinical progress.