Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo

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Citações na Scopus
9
Tipo de produção
article
Data de publicação
2022
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMERICAN CHEMICAL SOCIETY
Autores
KE, W.
CHANDLER, M.
CEDRONE, E.
WANG, J.
SHI, D.
TRUONG, N.
RICHARDSON, M.
Citação
NANO LETTERS, v.22, n.14, p.5961-5972, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The 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.
Palavras-chave
anticoagulation, aptamers, immunoquiescent, in vivo, kill-switch, RNA-DNA fibers
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