Gene expression changes upon activation of RIG-I by a minimal potent RIG-I ligand. Gene expression changes upon activation of RIG-I by a minimal potent RIG-I ligand

We have developed highly potent synthetic activators of the vertebrate immune system that specifically target the RIG-I receptor. When introduced into mice, a family of short, triphosphorylated Stem Loop RNAs (SLRs) induces a potent interferon response and the activation of specific genes essential for antiviral defense. Using RNAseq, we provide the first in-vivo genome-wide view of the expression networks that are initiated upon RIG-I activation. We observe that SLRs specifically induce type I interferons, subsets of interferon-stimulated genes (ISGs), and cellular remodeling factors. By contrast, poly(I:C), which binds and activates multiple RNA sensors, induces type III interferons and several unique ISGs. The short length (10-14 base pairs) and robust function of SLRs in mice demonstrate that RIG-I forms active signaling complexes without oligomerizing on RNA. These findings demonstrate that SLRs are potent therapeutic and investigative tools for targeted modulation of the innate immune system. Overall design: We have triplicate samples of spleens from mice treated with SLR10, SLR14, poly(I:C) and pppNS, we have duplicate samples of mice treated with jetPEI vehicle control, and we have triplicate samples of untreated control mice