Regulation of cGAS‐Mediated Immune Responses and Immunotherapy

Early detection of infectious nucleic acids released from invading pathogens by the innate immune system is critical for immune defense. Detection of these nucleic acids by host immune sensors and regulation of DNA sensing pathways have been significant interests in the past years. Here, current understandings of evolutionarily conserved DNA sensing cyclic GMP‐AMP (cGAMP) synthase (cGAS) are highlighted. Precise activation and tight regulation of cGAS are vital in appropriate innate immune responses, senescence, tumorigenesis and immunotherapy, and autoimmunity. Hence, substantial insights into cytosolic DNA sensing and immunotherapy of indispensable cytosolic sensors have been detailed to extend limited knowledge available thus far. This Review offers a critical, in‐depth understanding of cGAS regulation, cytosolic DNA sensing, and currently established therapeutic approaches of essential cytosolic immune agents for improved human health. The cGAS‐STING pathway is central to innate immunity and must be tightly regulated. cGAS performs essential roles in numerous immune functions such as DNA sensing, antiviral defense, antitumor immunity, senescence, and DNA repair. Aberrant cGAS activation leads to autoimmune and inflammatory diseases. Hence, several therapeutic approaches are used to regulate cGAS and related cytosolic sensors for improved human health.