适体
肿瘤坏死因子α
指数富集配体系统进化
肿瘤坏死因子受体1
受体
癌症研究
生物信息学
寡核苷酸
生物
细胞生物学
化学
药理学
免疫学
肿瘤坏死因子受体
分子生物学
生物化学
核糖核酸
基因
DNA
作者
Xiao Chu,Xinyue Du,Longhua Yang,Ziyi Wang,Yi Zhang,Xiaonan Wang,Lijun Dai,Jiangnan Zhang,Jie Liu,Nan Zhang,Yongxing Zhao,Hongzhou Gu
标识
DOI:10.1021/acsami.3c00131
摘要
Tumor necrosis factor-α (TNFα) inhibitors are widely used in treating autoimmune diseases like rheumatoid arthritis (RA). These inhibitors can presumably alleviate RA symptoms by blocking TNFα-TNF receptor 1 (TNFR1)-mediated pro-inflammatory signaling pathways. However, the strategy also interrupts the survival and reproduction functions conducted by TNFα-TNFR2 interaction and causes side effects. Thus, it is urgently needed to develop inhibitors that can selectively block TNFα-TNFR1 but not TNFα-TNFR2. Here, nucleic acid-based aptamers against TNFR1 are explored as potential anti-RA candidates. Through the systematic evolution of ligands by exponential enrichment (SELEX), two types of TNFR1-targeting aptamers were obtained, and their KD values are approximately 100-300 nM. In silico analysis shows that the binding interface of aptamer-TNFR1 highly overlapped with natural TNFα-TNFR1 binding. On the cellular level, the aptamers can exert TNFα inhibitory activity by binding to TNFR1. The anti-inflammatory efficiencies of aptamers were assessed and further enhanced using divalent aptamer constructs. These findings provide a new strategy to block TNFR1 for potential anti-RA treatment precisely.
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