Artificial aptamer that inhibits interleukin-23/interleukin-23 receptor interaction discovered via SELEX
Artificial aptamer that inhibits interleukin-23/interleukin-23 receptor interaction discovered via SELEX
复制标题
通过 SELEX 发现抑制白细胞介素 23/白细胞介素 23 受体相互作用的人工适体
DOI：
10.1016/j.bbrc.2022.05.012
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发表时间：
2022
影响因子：
3.1
通讯作者：
Kawakami Takashi
中科院分区：
文献类型：
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作者：
Takamori Yukio;Ando Takehiro;Sato Masashi;Vedi Santhana;Fuji Daisuke;Yokoyama Takumi;Tsukamoto Keita;Yamamoto Mizuki;Kawakami Takashi
促炎细胞因子白介素-23 （IL-23）和IL-23受体（IL-23R）之间的相互作用与银屑病、炎症性肠病和克罗恩病等炎症性自身免疫性疾病的发生有关。在这项研究中，我们通过指数富集（SELEX）对配体进行了系统的进化，以进行针对人IL-23的体外选择，并在最后一轮SELEX中观察到RNA序列的富集。化学发光检测和荧光成像显示，selex富集的RNA克隆与IL-23结合。使用IL-23 α (IL-23A)亚基（IL-23异源二聚体的一个组成部分）的定量聚合酶链反应为基础的下拉试验表明，RNA克隆与IL-23A结合，有利于自身免疫性疾病的治疗。我们还观察到新的IL-23结合RNA适体抑制IL-23和IL-23R之间的相互作用。因此，新的IL-23结合RNA适配体可用于IL-23的研究，并有可能用于IL-23的诊断和IL-23相关的炎症性自身免疫性疾病的治疗。
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) forin vitroselection 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.