4.6 Article

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

Journal

MOLECULES
Volume 26, Issue 21, Pages -

Publisher

MDPI
DOI: 10.3390/molecules26216525

Keywords

aptamer; binding motifs; ovarian cancer

Funding

  1. Department of Diagnostic and Interventional Imaging at the University of Texas Health Science Center at Houston (UT Health) and a grant from the National Institute of Health [U54 CA151668, UL1 TR000371)]

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The application of aptamers in cancer research is gaining importance due to their high specificity and low immunogenicity. Vimentin, an intermediate filament protein overexpressed in cancerous endothelial cells, has been targeted using thioated aptamers with high specificity. Future applications include targeted imaging and therapy using vimentin binding aptamers.
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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