A minimal RNA ligand for potent RIG-I activation in living mice

Linehan, M. M.; Dickey, T. H.; Molinari, E. S.; Fitzgerald, M. E.; Potapova, O.; Iwasaki, A.; Pyle, A. M.

doi:10.1101/178343

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bioRxiv · 10.1101/178343

A minimal RNA ligand for potent RIG-I activation in living mice

Linehan, M. M.·Dickey, T. H.·Molinari, E. S.·Fitzgerald, M. E.·Potapova, O.·Iwasaki, A.·Pyle, A. M.

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Abstract

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.

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Linehan, M. M., Dickey, T. H., Molinari, E. S., Fitzgerald, M. E., Potapova, O., Iwasaki, A., Pyle, A. M.. 2017-08-19. A minimal RNA ligand for potent RIG-I activation in living mice. https://doi.org/10.1101/178343

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