Innate immune RNA pattern recognition receptor (RNA PRR)

Innate immune RNA sensors are a diverse group of pattern recognition receptors (PRRs) that detect foreign or misplaced RNA molecules to initiate an immune response. This group primarily includes endosomal receptors like Toll-like receptors 7 and 8 (TLR7/8), which sense single-stranded RNA, and TLR3, which senses double-stranded RNA, as well as cytosolic sensors such as Retinoic acid-inducible gene I (RIG-I) and Melanoma differentiation-associated protein 5 (MDA5). In the context of mRNA therapeutics and vaccines, these sensors recognize the mRNA component as a pathogen-associated molecular pattern (PAMP), leading to the production of Type I interferons and pro-inflammatory cytokines. While this activation can provide a beneficial adjuvant effect for vaccines, excessive stimulation can lead to reactogenicity, injection site pain, or the inhibition of protein translation from the therapeutic mRNA itself. To manage these interactions, synthetic mRNA is often modified (e.g., using N1-methylpseudouridine) to evade detection by these sensors, thereby improving the safety and efficacy of the treatment.

Other names

Innate immune RNA sensorsRNA-sensing pattern recognition receptorsEndosomal RNA sensorsCytosolic RNA sensorsNucleic acid sensors

Agonism of these sensors triggers the production of Type I interferons and pro-inflammatory cytokines to enhance immune responses; antagonism or evasion (via mRNA modification) is used to reduce unwanted inflammation.