CGAS and infection: First, cyclic dinucleotides (CDNs) were identified as powerful STING-activating agents.5 Then, cGAMP (cyclic GMP-AMP) was identified as the mammalian CDN formed in response to cytosolic DNA and to infection by a DNA virus.9,12 These discoveries were followed by several independent reports that demonstrated that the enzyme cGAS (cyclic GMP-AMP synthase) was a cytosolic DNA sensor and was responsible for DNA-induced cGAMP production upstream of STING activation.10,11,56 The cytosolic DNA being sensed by cGAS can originate from various sources, including the nucleus57,58 and the mitochondria.59