The cGAS-STING intracellular DNA-sensing pathway has emerged as a key element of innate antiviral immunity and a promising therapeutic target. The existence of an innate immune sensor that can be activated by any double-stranded DNA (dsDNA) of any origin raises fundamental questions about how cGAS is regulated and how it responds to “foreign” DNA while maintaining tolerance to ubiquitous self-DNA. In this review, we summarize recent evidence implicating important roles for cGAS in the detection of foreign and self-DNA. We describe two recent and surprising insights into cGAS-STING biology: that cGAS is tightly tethered to the nucleosome and that the cGAMP product of cGAS is an immunotransmitter acting at a distance to control innate immunity. We consider how these advances influence our understanding of the emerging roles of cGAS in the DNA damage response (DDR), senescence, aging, and cancer biology. Finally, we describe emerging approaches to harness cGAS-STING biology for therapeutic benefit.

中文翻译：

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cGAS-STING 细胞内 DNA 传感途径的新前沿

cGAS-STING 细胞内 DNA 传感通路已成为先天抗病毒免疫的关键要素和有前途的治疗靶点。可以被任何来源的任何双链 DNA (dsDNA) 激活的先天免疫传感器的存在引发了关于 cGAS 如何调节以及它如何响应“外来”DNA 同时保持对普遍存在的自身 DNA 的耐受性的基本问题。在这篇综述中，我们总结了最近的证据，表明 cGAS 在检测外源 DNA 和自身 DNA 中发挥着重要作用。我们描述了关于 cGAS-STING 生物学的两个最新且令人惊讶的见解：cGAS 与核小体紧密相连，并且 cGAS 的 cGAMP 产物是一种免疫递质，可远距离控制先天免疫。我们思考这些进展如何影响我们对 cGAS 在 DNA 损伤反应 (DDR)、衰老和癌症生物学中的新兴作用的理解。最后，我们描述了利用 cGAS-STING 生物学获得治疗效果的新兴方法。