Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

Abstract

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.

• Authors: Si-Kun Guo, Chu-Xiao Liu, Yi-Feng Xu, Xiao Wang, Fang Nan, Youkui Huang, Siqi Li, Shan Nan, Ling Li, Edo Kon, Chen Li, Meng-Yuan Wei, Rina Su, Jia Wei, Shiguang Peng, Nitay Ad-El, Jiaquan Liu, Dan Peer, Ting Chen, Li Yang, Ling-Ling Chen
• Journal: Nature biotechnology (Nat Biotechnol) (Apr 23 2024) ISSN: 1546-1696 [Electronic] United States
• PMID: 38653797 (Publication Type: Journal Article)
• Copyright: © 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.