4.6 Article

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

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.05.012

Keywords

Interleukin-23; Interleukin-23 receptor; SELEX; Aptamer; Inflammatory autoimmune disease

Funding

  1. JSPS [15H05372, 15K13751, 21K06475, JPMJPR1685]
  2. MEXT Leading Initiative for Excellent Young Researchers, Japan
  3. Heiwa Nakajima Foundation, Japan
  4. JST PRESTO, Japan [15KT0071]

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The RNA aptamer selected against IL-23 through SELEX can bind to IL-23 and inhibit interaction between IL-23 and IL-23R, showing potential for the treatment of inflammatory autoimmune diseases.
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.(c) 2022 Elsevier Inc. All rights reserved.

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