Anti-IL-4Rα aptamer reduces IL-4 signalling and formation of nasal polyps.

Background: Aptamers are RNA- or DNA-based oligomers with high protein-specific binding properties that have demonstrated effectiveness in targeting various proteins and treating diseases such as cancer. However, their application in regulating chronic respiratory diseases, such as chronic rhinosinusitis, is not well established. Methods: In this study, we used the anti-IL-4Rα aptamer (anti-IL-4Rα apt) to investigate its impact on IL-4 signalling and related T-helper 2 (Th2)-type inflammation in nasal polyp tissue. To achieve this, we treated nasal polyp tissue extracted from chronic rhinosinusitis with nasal polyps (CRSwNP) patients who had undergone polypectomy with the anti-IL-4Rα apt. Furthermore, to evaluate the effects of the anti-IL-4Rα apt on NP formation, we established an eosinophilic mouse model of CRSwNP to mimic the Th2 inflammatory pathogenesis observed in CRSwNP. Results: Interestingly, we observed that treatment with anti-IL-4Rα apt resulted in a significant reduction in IL-4-STAT6 signalling and Th2-mediated inflammation, as demonstrated by an ∼2-fold decrease in the levels of IL-4Rα, phosphorylated STAT6 (p-STAT6) and GATA3 in treated nasal polyp (NP) tissues compared to the untreated uncinate process (p<0.001). Notably, we observed that the administration of the anti-IL-4Rα apt effectively reduced NP formation and Th2-mediated inflammation, as shown by an ∼3-fold reduction in the percentages of IL-4Rα, p-STAT6 and GATA3 positive cells in the nasal tissues of this mouse model (p<0.001). Conclusion: Given that the anti-IL-4Rα apt demonstrated comparable efficacy to dupilumab - an anti-IL-4Rα therapy proven effective for CRSwNP - this research highlights the potential therapeutic efficacy of aptamers in managing chronic inflammatory conditions such as those seen in CRSwNP.