Ribo– RNA-seq of psoriasis mouse model
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 evaluate the circRNA-PKR axis in psoriasis , we established a psoriasis mouse (C57BL/6) model via IMQ (imiquimod) treatment at day (D) 0, 1, 2, 3, 5. Then we conducted total RNA sequencing of mice spleens at day 0,1,2,5 following IMQ treatment. Of note, each RNA sequencing sample comprised total RNA extracted from two spleens of two mice. Each examined time point has two repeats, and each repeat includes 2 biologically independent mice.