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通过 SELEX 发现的抑制白细胞介素-23/白细胞介素-23 受体相互作用的人工适体。

Artificial aptamer that inhibits interleukin-23/interleukin-23 receptor interaction discovered via SELEX.

机构信息

Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.

Department of Life and Environmental Sciences, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.

出版信息

Biochem Biophys Res Commun. 2022 Jul 23;614:17-21. doi: 10.1016/j.bbrc.2022.05.012. Epub 2022 May 6.

Abstract

Interaction between the pro-inflammatory cytokine interleukin-23 (IL-23) and IL-23 receptor (IL-23R) is related to the development of inflammatory autoimmune diseases such as psoriasis, inflammatory bowel disease, and Crohn's disease. In this study, we conducted systematic evolution of ligands by exponential enrichment (SELEX) for in vitro selection against human IL-23 and observed RNA sequence enrichment in the final SELEX round. IL-23-pull-down assay by chemiluminescence detection and fluorescence imaging demonstrated that SELEX-enriched RNA clone bound to IL-23. Quantitative polymerase chain reaction-based pull-down assay using the IL-23 alpha (IL-23A) subunit, a component of the IL-23 heterodimer, indicated that the RNA clone bound to IL-23A, which is favorable for autoimmune disease treatment. We also observed that the novel IL-23-binding RNA aptamer inhibited interaction between IL-23 and IL-23R. Thus, the novel IL-23-binding RNA aptamer can be used for IL-23 studies and has potential to be used for IL-23 diagnosis and IL-23-related inflammatory autoimmune disease treatment.

摘要

白细胞介素-23(IL-23)和 IL-23 受体(IL-23R)之间的相互作用与炎症性自身免疫性疾病的发展有关,如银屑病、炎症性肠病和克罗恩病。在这项研究中,我们进行了体外筛选针对人 IL-23 的配体的系统进化的配体指数富集(SELEX),并观察了最终 SELEX 轮中的 RNA 序列富集。通过化学发光检测和荧光成像的 IL-23 下拉测定表明,SELEX 富集的 RNA 克隆与 IL-23 结合。使用 IL-23 异二聚体的组成部分 IL-23A 亚基的基于聚合酶链反应的下拉测定表明,该 RNA 克隆与 IL-23A 结合,这有利于自身免疫性疾病的治疗。我们还观察到,新型 IL-23 结合 RNA 适体抑制了 IL-23 与 IL-23R 之间的相互作用。因此,新型 IL-23 结合 RNA 适体可用于 IL-23 研究,并有可能用于 IL-23 诊断和 IL-23 相关炎症性自身免疫性疾病的治疗。

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