circSHAPE-MaP of EPIC

Efforts to advance RNA aptamers as a novel therapeutic modality have been limited by their susceptibilty to degradation and immunogenicity. In a previous study, we demonstrated synthesized double-stranded circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated Protein Kinase R (PKR). Here, we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon alpha (IFNa)/dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes. Overall design: To exclude the effect of LNP encapsulation and biotin/Cy5 labeling on EPIC structure, we perform circSHAPE-MaP of LNP encapsulated EPIC, biotin/Cy5 labeled EPIC and EPIC among 3 biological replicates. Each samples has 2 techonical repeats. To understand interacting region of EPIC when binding with PKR, we perform circSHAPE-MaP of EPIC with or without PKR.