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3p-RNA (5'-triphosphate RNA) is a synthetic double-stranded RNA molecule containing a 5'-triphosphate group that acts as a potent agonist of the cytosolic pattern recognition receptor retinoic acid-inducible gene I (RIG-I). Upon binding to RIG-I, 3p-RNA triggers a conformational change that activates the mitochondrial antiviral-signaling protein (MAVS) pathway, leading to the downstream activation of IRF3 and NF-κB. This cascade induces the robust production of type I interferons (IFN-α and IFN-β) and proinflammatory cytokines, thereby remodeling the tumor microenvironment and promoting adaptive antitumor immunity. Additionally, 3p-RNA has been shown to directly activate oligoadenylate synthetase 1 (OAS1) and RNase L, as well as protein kinase R (PKR), to induce translational arrest and tumor cell apoptosis. It is widely utilized as a research reagent and is being investigated preclinically as an immunotherapeutic agent for various cancers, including hepatocellular carcinoma and pancreatic ductal adenocarcinoma, often in combination with immune checkpoint inhibitors or CAR-T cell therapies.
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