Optogenetic technologies have transformed our ability to precisely control biological processes in time and space. Yet, current eukaryotic optogenetic systems are limited by large or complex optogenetic modules, long illumination times, low tissue penetration or slow activation and deactivation kinetics. Here, we report a red/far-red light-mediated and miniaturized Δphytochrome A (ΔPhyA)-based photoswitch (REDMAP) system based on the plant photoreceptor PhyA, which rapidly binds the shuttle protein far-red elongated hypocotyl 1 (FHY1) under illumination with 660-nm light with dissociation occurring at 730 nm. We demonstrate multiple applications of REDMAP, including dynamic on/off control of the endogenous Ras/Erk mitogen-activated protein kinase (MAPK) cascade and control of epigenetic remodeling using a REDMAP-mediated CRISPR–nuclease-deactivated Cas9 (CRISPR–dCas9) (REDMAP_cas) system in mice. We also demonstrate the utility of REDMAP tools for in vivo applications by activating the expression of transgenes delivered by adeno-associated viruses (AAVs) or incorporated into cells in microcapsules implanted into mice, rats and rabbits illuminated by light-emitting diodes (LEDs). Further, we controlled glucose homeostasis in type 1 diabetic (T1D) mice and rats using REDMAP to trigger insulin expression. REDMAP is a compact and sensitive tool for the precise spatiotemporal control of biological activities in animals with applications in basic biology and potentially therapy.

光遗传学技术改变了我们在时间和空间上精确控制生物过程的能力。然而，当前的真核光遗传学系统受到大型或复杂的光遗传学模块、长光照时间、低组织渗透或慢激活和失活动力学的限制。在这里，我们报告了一种基于植物光感受器 PhyA 的红/远红光介导和小型化 Δphytochrome A (ΔPhyA) 基光开关 (REDMAP) 系统，该系统可在以下条件下快速结合穿梭蛋白远红伸长下胚轴 1 (FHY1)用 660 nm 光照射，解离发生在 730 nm。我们演示了 REDMAP 的多种应用，_cas ) 小鼠系统。我们还通过激活腺相关病毒 (AAV) 传递的转基因表达或植入小鼠、大鼠和兔子体内的微胶囊细胞中的细胞，展示了 REDMAP 工具在体内应用中的效用，这些微胶囊由发光二极管 (LED) 照明。此外，我们使用 REDMAP 触发胰岛素表达来控制 1 型糖尿病 (T1D) 小鼠和大鼠的葡萄糖稳态。REDMAP 是一种紧凑而灵敏的工具，用于对动物的生物活动进行精确的时空控制，在基础生物学和潜在治疗中都有应用。