Nature biotechnology · 2024
Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.
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Guo Si-Kun, Liu Chu-Xiao, Xu Yi-Feng, Wang Xiao, Nan Fang, Huang Youkui, Li Siqi, Nan Shan, Li Ling, Kon Edo, Li Chen, Wei Meng-Yuan, Su Rina, Wei Jia, Peng Shiguang, Ad-El Nitay, Liu Jiaquan, Peer Dan, Chen Ting, Yang Li, Chen Ling-Ling
Аннотация
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.