Nucleic Acid Sensors as Therapeutic Targets for Human Disease

Innate immune sensors that detect nucleic acids are attractive targets for therapeutic intervention because of their diverse roles in many disease processes. In detecting RNA and DNA from either self or non-self, nucleic acid sensors mediate the pathogenesis of many autoimmune and inflammatory condi...

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Published inImmunity (Cambridge, Mass.) Vol. 53; no. 1; pp. 78 - 97
Main Authors McWhirter, Sarah M., Jefferies, Caroline A.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 14.07.2020
Elsevier Limited
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Summary:Innate immune sensors that detect nucleic acids are attractive targets for therapeutic intervention because of their diverse roles in many disease processes. In detecting RNA and DNA from either self or non-self, nucleic acid sensors mediate the pathogenesis of many autoimmune and inflammatory conditions. Despite promising pre-clinical data and investigational use in the clinic, relatively few drugs targeting nucleic acid sensors are approved for therapeutic use. Nevertheless, there is growing appreciation for the untapped potential of nucleic acid sensors as therapeutic targets, driven by the need for better therapies for cancer, infectious diseases, and autoimmune disorders. This review highlights the diverse mechanisms by which nucleic acid sensors are activated and exert their biological effects in the context of various disease settings. We discuss current therapeutic strategies utilizing agonists and antagonists targeting nucleic acid sensors to treat infectious disease, cancer, and autoimmune and inflammatory disorders. McWhirter and Jefferies review the mechanisms that link nucleic acid sensors, including TLR, RLR, and cGAS/STING, to infectious disease, cancer, and autoimmune and inflammatory disorders. The authors describe agonists and antagonists targeting nucleic acid sensors and emerging therapeutic strategies currently under investigation.
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ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2020.04.004