Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing 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-α and 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.

RNA适体作为一种新的治疗方式的发展受到其易降解和免疫原性的限制。在之前的一项研究中，我们证明了合成的含有短双链区域的环状 RNA (ds-cRNA)，其针对 dsRNA 激活的蛋白激酶 R (PKR) 具有最小的免疫原性。在这里，我们测试了 ds-cRNA 在咪喹莫特诱导的牛皮癣小鼠模型中的治疗潜力。我们发现 ds-cRNA 的基因补充会抑制 PKR，从而减轻下游干扰素-α 和 dsRNA 信号并减弱银屑病表型。通过脂质纳米颗粒将 ds-cRNA 递送至脾脏会减弱所检查的脾细胞中的 PKR 活性，从而导致表皮厚度减少。这些发现表明，ds-cRNA 代表了一种有前途的方法，可以减轻 PKR 过度激活以达到治疗目的。