biostudies-literatureUnknown15(32)Yao LIL-6 (interleukin-6) is an essential cytokine that participates in many inflammatory and immune responses, and disrupting the interaction between IL-6 and its receptor sIL-6R (soluble form of IL-6 receptor) represents a promising treatment strategy for inflammation and related diseases. Herein we report the first-ever effort of evolving a bispecific circular aptamer, named CIL-6A6-1, that is capable of binding both IL-6 and sIL-6R with nanomolar affinities and is stable in serum for more than 48 hours. CIL-6A6-1 can effectively block the IL-6/sIL-6R interaction and significantly inhibit cell inflammation. Most importantly, this bispecific aptamer is much more effective than aptamers that bind IL-6 and sIL-6R alone as well as tocilizumab, a commercially available humanized monoclonal antiboChemical science13011-13020https://www.ebi.ac.uk/biostudies/studies/S-EPMC11323322biostudies-literatureEvolution of a bispecific G-quadruplex-forming circular aptamer to block IL-6/sIL-6R interaction for inflammation inhibition.PMC11323322Yao LLi YZheng LQu HLiu SMao YWang LfalseEvolution of a bispecific G-quadruplex-forming circular aptamer to block IL-6/sIL-6R interaction for inflammation inhibition.IL-6 (interleukin-6) is an essential cytokine that participates in many inflammatory and immune responses, and disrupting the interaction between IL-6 and its receptor sIL-6R (soluble form of IL-6 receptor) represents a promising treatment strategy for inflammation and related diseases. Herein we report the first-ever effort of evolving a bispecific circular aptamer, named CIL-6A6-1, that is capable of binding both IL-6 and sIL-6R with nanomolar affinities and is stable in serum for more than 48 hours. CIL-6A6-1 can effectively block the IL-6/sIL-6R interaction and significantly inhibit cell inflammation. Most importantly, this bispecific aptamer is much more effective than aptamers that bind IL-6 and sIL-6R alone as well as tocilizumab, a commercially available humanized monoclonal antibo2024-01-01T00:00:00Z2024 Aug2025-04-19T20:40:55.491Z2025-04-19T20:40:55.491ZS-EPMC113233223914878610.1039/d4sc02183e