Ribo– RNA-seq of psoriasis mouse model delivered (i.v.) EPIC by LNP at D1.5
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 investigate whether delivery of in vitro synthesized RNA circle EPIC can affect endogenous circRNAs expression, we established psoriasis mouse model via IMQ (imiquimod) treatment at D0 and D1, and delivered (i.v.) EPIC by LNP at D1.5. We then performed total RNA sequencing of mouse (C57BL/6) spleens at D2.5 after intravenous injection. Each sequencing sample contained RNA isolated from spleen of one mouse.