2. Academic Validation
  3. Targeting Tumor Necrosis Factor Receptor 1 with Selected Aptamers for Anti-Inflammatory Activity

Targeting Tumor Necrosis Factor Receptor 1 with Selected Aptamers for Anti-Inflammatory Activity

  • ACS Appl Mater Interfaces. 2023 Feb 22. doi: 10.1021/acsami.3c00131.
Xiao Chu 1 2,  Xinyu Du 2,  Longhua Yang 1,  Ziyi Wang 1,  Yi Zhang 1,  Xiaonan Wang 1,  Lijun Dai 1,  Jiangnan Zhang 1,  Jie Liu 2,  Nan Zhang 1,  Yongxing Zhao 1,  Hongzhou Gu 2 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 2 Fudan University Shanghai Cancer Center, and Institutes of Biomedical Sciences, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, China.
  • 3 School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
PMID: 36812453 DOI: 10.1021/acsami.3c00131
Abstract

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.

Keywords

SELEX; TNFR1; anti-inflammation; aptamer; molecular simulation; rheumatoid arthritis.

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