The ability to remote control the expression of therapeutic genes in mammalian cells in order to treat disease is a central goal of synthetic biology‐inspired therapeutic strategies. Furthermore, optogenetics, a combination of light and genetic sciences, provides an unprecedented ability to use light for precise control of various cellular activities with high spatiotemporal resolution. Recent work to combine optogenetics and therapeutic synthetic biology has led to the engineering of light‐controllable designer cells, whose behavior can be regulated precisely and noninvasively. This Review focuses mainly on non‐neural optogenetic systems, which are often used in synthetic biology, and their applications in genetic programing of mammalian cells. Here, a brief overview of the optogenetic tool kit that is available to build light‐sensitive mammalian cells is provided. Then, recently developed strategies for the control of designer cells with specific biological functions are summarized. Recent translational applications of optogenetically engineered cells are also highlighted, ranging from in vitro basic research to in vivo light‐controlled gene therapy. Finally, current bottlenecks, possible solutions, and future prospects for optogenetics in synthetic biology are discussed.

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光控哺乳动物细胞及其在合成生物学中的治疗应用

远程控制哺乳动物细胞中治疗基因的表达以治疗疾病的能力是合成生物学启发的治疗策略的核心目标。此外，光遗传学作为光和遗传科学的结合，提供了前所未有的能力，可以利用光以高时空分辨率精确控制各种细胞活动。最近将光遗传学和治疗合成生物学相结合的工作导致了光控设计细胞的工程化，其行为可以精确且非侵入性地调节。本综述主要关注合成生物学中常用的非神经光遗传学系统及其在哺乳动物细胞遗传编程中的应用。这里提供了可用于构建光敏哺乳动物细胞的光遗传学工具套件的简要概述。然后，总结了最近开发的控制具有特定生物学功能的设计细胞的策略。还强调了光遗传学工程细胞最近的转化应用，从体外基础研究到体内光控基因治疗。最后，讨论了光遗传学在合成生物学中当前的瓶颈、可能的解决方案和未来前景。