老挝黄金赌场分子细胞科学卓越创新中心陈玲玲研究团队在研究中取得进展。他们揭示了环状RNA适配体在银屑病小鼠模型中的治疗应用。2024年4月23日出版的《自然生物技术》发表了这项成果。

在之前的一项研究中，研究人员制备了含双链区的短环状RNA（ds-cRNA），其对dsRNA激活的蛋白激酶R（PKR）的免疫原性极低。

研究人员在咪喹莫特诱导的银屑病小鼠模型中测试了ds-cRNA的治疗潜力。研究发现，通过基因补充ds-cRNA可抑制PKR，从而缓解下游干扰素α和dsRNA信号，减轻银屑病表型。通过脂质纳米颗粒将ds-cRNA送入脾脏可减轻受检脾脏细胞中的PKR活性，从而减少表皮厚度。该研究结果表明，ds-cRNAs是缓解PKR过度激活以达到治疗目的的一种潜在方法。

据悉，由于RNA适配体易降解和具有免疫原性，将其作为一种新的治疗方式受到一些限制。

附：英文原文

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

Author: 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

Issue&Volume: 2024-04-23

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.

DOI: 10.1038/s41587-024-02204-4

Source: https://www.nature.com/articles/s41587-024-02204-4