Innate immune double-stranded RNA sensors (dsRNA sensors)

Innate immune double-stranded RNA (dsRNA) sensors are a specialized class of pattern recognition receptors (PRRs) that detect dsRNA, a key molecular signature of viral replication and cellular stress. This group comprises several distinct proteins, including the endosomal Toll-like receptor 3 (TLR3) and cytosolic sensors such as the RIG-I-like receptors (RIG-I and MDA5), protein kinase R (PKR), and 2'-5'-oligoadenylate synthetase (OAS). Upon binding to dsRNA, these sensors trigger signaling cascades—primarily through the adapter proteins TRIF or MAVS—that culminate in the production of type I interferons (IFNs) and pro-inflammatory cytokines, which orchestrate the host's antiviral defense and bridge innate and adaptive immunity. In therapeutic development, these sensors are primarily targeted by agonists, such as Rintatolimod and Poly-ICLC, to induce a "viral mimicry" state in cancer cells, thereby enhancing the efficacy of immunotherapies and promoting antitumor immune responses. Conversely, the aberrant activation of these sensors by endogenous "self" dsRNA is implicated in the pathogenesis of autoimmune and autoinflammatory disorders, such as Aicardi-Goutières syndrome, making them targets for inhibitory strategies. Therapeutic challenges include managing systemic inflammation and the risk of cytokine release syndrome associated with potent immune activation.

Other names

Pattern recognition receptors for dsRNARNA-sensing pattern recognition receptorsCytosolic RNA sensorsEndosomal RNA sensorsdsRNA-binding proteins involved in innate immunity

Agonism of pattern recognition receptors to induce type I interferon production and activate innate and adaptive immune responses.