Anticoagulant Activity of Nucleic Acid Nanoparticles (NANPs) Assessed by Thrombin Generation Dynamics on a Fully Automated System.

Autor:	de Freitas Saito R; Comprehensive Center for Precision Oncology, Centro de Investigação Translacional em Oncologia (LIM24), Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brazil. renata.saito@hc.fm.usp.br., Barion BG; Laboratório de Hemostasia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil., da Rocha TRF; Laboratório de Hemostasia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil., Rolband A; University of North Carolina, Charlotte, NC, USA., Afonin KA; University of North Carolina, Charlotte, NC, USA., Chammas R; Comprehensive Center for Precision Oncology, Centro de Investigação Translacional em Oncologia (LIM24), Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brazil. rchammas@usp.br.
Jazyk:	angličtina
Zdroj:	Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2023; Vol. 2709, pp. 319-332.
DOI:	10.1007/978-1-0716-3417-2_23
Abstrakt:	Rapidly reversible anticoagulant agents have great clinical potential. Oligonucleotide-based anticoagulant agents are uniquely positioned to fill this clinical niche, as they are able to be deactivated through the introduction of the reverse complement oligo. Once the therapeutic and the antidote oligos meet in solution, they are able to undergo isothermal reassociation to form short, inactive, duplexes that are rapidly secreted via filtration by the kidneys. The formation of the duplexes interrupts the structure of the anticoagulant oligo, allowing normal coagulation to be restored. To effectively assess these new anticoagulants, a variety of methods may be employed. The measurement of thrombin generation (TG) reflects the overall capacity of plasma to produce active thrombin and provides a strong contribution to identifying new anticoagulant drugs, including DNA/RNA thrombin binding aptamer carrying fibers which are used through this chapter as an example. Here we describe the TG assessed by Calibrated Automated Thrombogram (CAT) assay in a fully automated system. This method is based on the detection of TG in plasma samples by measuring fluorescent signals released from a quenched fluorogenic thrombin substrate and the subsequent conversion of these signals in TG curves. (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze:	MEDLINE
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