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In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate

Dabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for a number of blood thrombosis conditions, prevention of strokes and systemic emboli among patients with atrial fibrillation. It provides safe and adequate anticoagulation for prevention and treatment of thrombus in sever...

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Autores principales: Aljohani, Maher M., Chinnappan, Raja, Eissa, Shimaa, Alsager, Omar A., Weber, Karina, Cialla-May, Dana, Popp, Jürgen, Zourob, Mohammed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125329/
https://www.ncbi.nlm.nih.gov/pubmed/30185972
http://dx.doi.org/10.1038/s41598-018-31327-3
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author Aljohani, Maher M.
Chinnappan, Raja
Eissa, Shimaa
Alsager, Omar A.
Weber, Karina
Cialla-May, Dana
Popp, Jürgen
Zourob, Mohammed
author_facet Aljohani, Maher M.
Chinnappan, Raja
Eissa, Shimaa
Alsager, Omar A.
Weber, Karina
Cialla-May, Dana
Popp, Jürgen
Zourob, Mohammed
author_sort Aljohani, Maher M.
collection PubMed
description Dabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for a number of blood thrombosis conditions, prevention of strokes and systemic emboli among patients with atrial fibrillation. It provides safe and adequate anticoagulation for prevention and treatment of thrombus in several clinical settings. However, anticoagulation therapy can be associated with an increased risk of bleeding. There is a lack of specific laboratory tests to determine the level of this drug in blood. This is considered the most important obstacles of using this medication, particularly for patients with trauma, drug toxicity, in urgent need for surgical interventions or uncontrolled bleeding. In this work, we performed Systematic evolution of ligands by exponential enrichment (SELEX) to select specific DNA aptamers against dabigatran etexilate. Following multiple rounds of selection and enrichment with a randomized 60-mer DNA library, specific DNA aptamers for dabigatran were selected. We investigated the affinity and specificity of generated aptamers to the drug showing dissociation constants (K(d)) ranging from 46.8–208 nM. The most sensitive aptamer sequence was selected and applied in an electrochemical biosensor to successfully achieve 0. 01 ng/ml level of detection of the target drug. With further improvement of the assay and optimization, these aptamers would replace conventional antibodies for developing detection assays in the near future.
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spelling pubmed-61253292018-09-10 In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate Aljohani, Maher M. Chinnappan, Raja Eissa, Shimaa Alsager, Omar A. Weber, Karina Cialla-May, Dana Popp, Jürgen Zourob, Mohammed Sci Rep Article Dabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for a number of blood thrombosis conditions, prevention of strokes and systemic emboli among patients with atrial fibrillation. It provides safe and adequate anticoagulation for prevention and treatment of thrombus in several clinical settings. However, anticoagulation therapy can be associated with an increased risk of bleeding. There is a lack of specific laboratory tests to determine the level of this drug in blood. This is considered the most important obstacles of using this medication, particularly for patients with trauma, drug toxicity, in urgent need for surgical interventions or uncontrolled bleeding. In this work, we performed Systematic evolution of ligands by exponential enrichment (SELEX) to select specific DNA aptamers against dabigatran etexilate. Following multiple rounds of selection and enrichment with a randomized 60-mer DNA library, specific DNA aptamers for dabigatran were selected. We investigated the affinity and specificity of generated aptamers to the drug showing dissociation constants (K(d)) ranging from 46.8–208 nM. The most sensitive aptamer sequence was selected and applied in an electrochemical biosensor to successfully achieve 0. 01 ng/ml level of detection of the target drug. With further improvement of the assay and optimization, these aptamers would replace conventional antibodies for developing detection assays in the near future. Nature Publishing Group UK 2018-09-05 /pmc/articles/PMC6125329/ /pubmed/30185972 http://dx.doi.org/10.1038/s41598-018-31327-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Aljohani, Maher M.
Chinnappan, Raja
Eissa, Shimaa
Alsager, Omar A.
Weber, Karina
Cialla-May, Dana
Popp, Jürgen
Zourob, Mohammed
In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate
title In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate
title_full In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate
title_fullStr In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate
title_full_unstemmed In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate
title_short In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate
title_sort in vitro selection of specific dna aptamers against the anti-coagulant dabigatran etexilate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125329/
https://www.ncbi.nlm.nih.gov/pubmed/30185972
http://dx.doi.org/10.1038/s41598-018-31327-3
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