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

  1. Author:
    Ke, Weina
    Chandler, Morgan [ORCID]
    Cedrone,Edward
    Saito, Renata F
    Rangel, Maria Cristina
    de Souza Junqueira, Mara
    Wang, Jian
    Shi, Da
    Truong, Nguyen
    Richardson, Melina
    Rolband, Lewis A [ORCID]
    Dréau, Didier
    Bedocs, Peter
    Chammas, Roger
    Dokholyan, Nikolay V
    Dobrovolskaia,Marina [ORCID]
    Afonin, Kirill A [ORCID]

  2. Author Address

    Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, United States., Nanotechnology Characterization Lab., Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland 21702, United States., Centro de Investiga 231; 227;o Translacional em Oncologia (LIM24), Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de S 227;o Paulo and Instituto do C 226;ncer do Estado de S 227;o Paulo, S 227;o Paulo, SP 01246-903, Brazil., Department of Pharmacology, Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States., Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, United States., Department of Anesthesiology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, United States., Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland 20817, United States., Department of Chemistry, Department of Biomedical Engineering, Penn State University, University Park, Pennsylvania 16802, United States.,
    1. Year: 2022
    2. Date: Jul 05
    3. Epub Date: 2022 07 05
  2. Journal: Nano Letters
  4. Type of Article: Article
  1. Abstract:

    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.

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External Sources

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  2. DOI: 10.1021/acs.nanolett.2c02019
  3. PMID: 35786891

Library Notes

  1. Fiscal Year: FY2021-2022
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