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Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer

The application of aptamers in biomedicine is emerging as an essential technology in the field of cancer research. As small single-stranded DNA or RNA ligands with high specificity and low immunogenicity for their targets, aptamers provide many advantages in cancer therapeutics over protein-based mo...

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Autores principales: Costello, Andrea M., Elizondo-Riojas, Miguel-Angel, Li, Xin, Volk, David E., Pillai, Anil K., Wang, Hongyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588432/
https://www.ncbi.nlm.nih.gov/pubmed/34770931
http://dx.doi.org/10.3390/molecules26216525
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author Costello, Andrea M.
Elizondo-Riojas, Miguel-Angel
Li, Xin
Volk, David E.
Pillai, Anil K.
Wang, Hongyu
author_facet Costello, Andrea M.
Elizondo-Riojas, Miguel-Angel
Li, Xin
Volk, David E.
Pillai, Anil K.
Wang, Hongyu
author_sort Costello, Andrea M.
collection PubMed
description The application of aptamers in biomedicine is emerging as an essential technology in the field of cancer research. As small single-stranded DNA or RNA ligands with high specificity and low immunogenicity for their targets, aptamers provide many advantages in cancer therapeutics over protein-based molecules, such as antibodies. Vimentin is an intermediate filament protein that is overexpressed in endothelial cells of cancerous tissue. High expression levels of vimentin have been associated with increased capacity for migration and invasion of the tumor cells. We have selected and identified thioated aptamers with high specificity for vimentin using human ovarian cancer tissues. Tentative binding motifs were chosen for two vimentin aptamers based on predicted secondary structures. Each of these shorter, tentative binding motifs was synthesized, purified, and characterized via cell binding assays. Two vimentin binding motifs with high fidelity binding were selected and further characterized via cell and tissue binding assays, as well as flow cytometric analysis. The equilibrium binding constants of these small thioated aptamer constructs were also determined. Future applications for the vimentin binding aptamer motifs include conjugation of the aptamers to synthetic dyes for use in targeted imaging and therapy, and ultimately more detailed and precise monitoring of treatment response and tumor progression in ovarian pathology.
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spelling pubmed-85884322021-11-13 Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer Costello, Andrea M. Elizondo-Riojas, Miguel-Angel Li, Xin Volk, David E. Pillai, Anil K. Wang, Hongyu Molecules Article The application of aptamers in biomedicine is emerging as an essential technology in the field of cancer research. As small single-stranded DNA or RNA ligands with high specificity and low immunogenicity for their targets, aptamers provide many advantages in cancer therapeutics over protein-based molecules, such as antibodies. Vimentin is an intermediate filament protein that is overexpressed in endothelial cells of cancerous tissue. High expression levels of vimentin have been associated with increased capacity for migration and invasion of the tumor cells. We have selected and identified thioated aptamers with high specificity for vimentin using human ovarian cancer tissues. Tentative binding motifs were chosen for two vimentin aptamers based on predicted secondary structures. Each of these shorter, tentative binding motifs was synthesized, purified, and characterized via cell binding assays. Two vimentin binding motifs with high fidelity binding were selected and further characterized via cell and tissue binding assays, as well as flow cytometric analysis. The equilibrium binding constants of these small thioated aptamer constructs were also determined. Future applications for the vimentin binding aptamer motifs include conjugation of the aptamers to synthetic dyes for use in targeted imaging and therapy, and ultimately more detailed and precise monitoring of treatment response and tumor progression in ovarian pathology. MDPI 2021-10-28 /pmc/articles/PMC8588432/ /pubmed/34770931 http://dx.doi.org/10.3390/molecules26216525 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Costello, Andrea M.
Elizondo-Riojas, Miguel-Angel
Li, Xin
Volk, David E.
Pillai, Anil K.
Wang, Hongyu
Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer
title Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer
title_full Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer
title_fullStr Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer
title_full_unstemmed Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer
title_short Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer
title_sort selection and characterization of vimentin-binding aptamer motifs for ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588432/
https://www.ncbi.nlm.nih.gov/pubmed/34770931
http://dx.doi.org/10.3390/molecules26216525
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