Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPKE, W.CHANDLER, M.CEDRONE, E.SAITO, R. F.RANGEL, M. C.JUNQUEIRA, M. De SouzaWANG, J.SHI, D.TRUONG, N.RICHARDSON, M.ROLBAND, L. A.DRéAU, D.BEDOCS, P.CHAMMAS, R.DOKHOLYAN, N. V.DOBROVOLSKAIA, M. A.AFONIN, K. A.2024-03-132024-03-132022NANO LETTERS, v.22, n.14, p.5961-5972, 20221530-6984https://observatorio.fm.usp.br/handle/OPI/58614The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a ""kill-switch""mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in vivo in comparison to free aptamers. Finally, we confirm the efficacy of the ""kill-switch""mechanism in vivo in murine and porcine models.engrestrictedAccessanticoagulationaptamersimmunoquiescentin vivokill-switchRNA-DNA fibersanimalsanticoagulantsaptamers, nucleotidehumansleukocytes, mononuclearmicenanoparticlesnucleic acidsswinethrombinbloodenzymesfiberslocks (fasteners)anticoagulant agentaptamernanoparticlenucleic acidthrombinanti-coagulationaptamersbio-moleculardna fiberimmunoquiescentin-vivokill-switchrna-dna fiberswitch mechanismuser friendlyanimalchemistryhumanmononuclear cellmousepigrnaarticleCopyright AMERICAN CHEMICAL SOCIETY10.1021/acs.nanolett.2c02019