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This research is based on a Systematic Evolution of Ligands by EXponential enrichment, also referred to as in vitroselection against the extracellular domain of human interleukin-17 receptor A (IL-17RA). Pull-down assay viaquantitative polymerase chain reaction and chemiluminescence detection showed that the cloned RNA with the enriched sequence bound to human IL-17RA and inhibited the interaction between IL-17RA and human interleukin-17A (IL-17A). We also revealed that the newly discovered IL-17RA-binding RNA aptamer bound to cellular IL-17RA, inhibited the cellular IL-17RA/IL-17A interaction, and antagonized cellular IL-17A signaling.Graphical AbstractNovel IL-17R-binding aptamer was discovered by SELEX, inhibited cellular interleukin-17/interleukin-17 receptor interaction and antagonized interleukin-17 signaling.