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 Yang; Ling Ling Chen

doi:10.1038/s41587-024-02204-4

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

Tel Aviv University

Research output: Contribution to journal › Article › peer-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 language	English
Article number	e1594
Pages (from-to)	236-246
Number of pages	11
Journal	Nature biotechnology
Volume	43
Issue number	2
DOIs	https://doi.org/10.1038/s41587-024-02204-4
State	Published - Feb 2025

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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Guo, S. K., Liu, C. X., Xu, Y. F., Wang, X., Nan, F., Huang, Y., Li, S., Nan, S., Li, L., Kon, E., Li, C., Wei, M. Y., Su, R., Wei, J., Peng, S., Ad-El, N., Liu, J., Peer, D., Chen, T., ... Chen, L. L. (2025). Therapeutic application of circular RNA aptamers in a mouse model of psoriasis. Nature biotechnology, 43(2), 236-246. Article e1594. https://doi.org/10.1038/s41587-024-02204-4

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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.",

author = "Guo, \{Si Kun\} and Liu, \{Chu Xiao\} and Xu, \{Yi Feng\} and Xiao Wang and Fang Nan and Youkui Huang and Siqi Li and Shan Nan and Ling Li and Edo Kon and Chen Li and Wei, \{Meng Yuan\} and Rina Su and Jia Wei and Shiguang Peng and Nitay Ad-El and Jiaquan Liu and Dan Peer and Ting Chen and Li Yang and Chen, \{Ling Ling\}",

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doi = "10.1038/s41587-024-02204-4",

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AU - Guo, Si Kun

AU - Liu, Chu Xiao

AU - Xu, Yi Feng

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AU - Nan, Fang

AU - Huang, Youkui

AU - Li, Siqi

AU - Nan, Shan

AU - Li, Ling

AU - Kon, Edo

AU - Li, Chen

AU - Wei, Meng Yuan

AU - Su, Rina

AU - Wei, Jia

AU - Peng, Shiguang

AU - Ad-El, Nitay

AU - Liu, Jiaquan

AU - Peer, Dan

AU - Chen, Ting

AU - Yang, Li

AU - Chen, Ling Ling

PY - 2025/2

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AB - 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.

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JO - Nature biotechnology

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

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