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

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 YangLing Ling Chen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number3892
JournalNature Biotechnology
DOIs
StatePublished - Apr 23 2024

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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