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Mol Ther Nucleic Acids. 2019 Sep 6;17:63-77. doi: 10.1016/j.omtn.2019.05.006. Epub 2019 May 24.

RNA Aptamers Targeting Integrin α5β1 as Probes for Cyto- and Histofluorescence in Glioblastoma.

Author information

1
CNRS, UMR 7242, Biotechnologie et Signalisation Cellulaire, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, Université de Strasbourg, 67400 Illkirch-Graffenstaden, France.
2
CNRS, UMR 7021, Laboratoire de Bioimagerie et Pathologies, Tumoral Signaling and Therapeutic Targets, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France.
3
CNRS, UMR 7021, Laboratoire de Bioimagerie et Pathologies, Tumoral Signaling and Therapeutic Targets, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France; Département de Pharmacie, Centre de Lutte Contre le Cancer Paul Strauss, 67000 Strasbourg, France.
4
EA 3430, Progression Tumorale et Micro-environnement, Approches Translationnelles et Épidémiologie, Université de Strasbourg, 67000 Strasbourg, France.
5
CNRS, UMR 7199, Laboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France.
6
CNRS, UMR 7021, Laboratoire de Bioimagerie et Pathologies, Tumoral Signaling and Therapeutic Targets, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France. Electronic address: laurence.choulier@unistra.fr.

Abstract

Nucleic acid aptamers are often referred to as chemical antibodies. Because they possess several advantages, like their smaller size, temperature stability, ease of chemical modification, lack of immunogenicity and toxicity, and lower cost of production, aptamers are promising tools for clinical applications. Aptamers against cell surface protein biomarkers are of particular interest for cancer diagnosis and targeted therapy. In this study, we identified and characterized RNA aptamers targeting cells expressing integrin α5β1. This αβ heterodimeric cell surface receptor is implicated in tumor angiogenesis and solid tumor aggressiveness. In glioblastoma, integrin α5β1 expression is associated with an aggressive phenotype and a decrease in patient survival. We used a complex and original hybrid SELEX (selective evolution of ligands by exponential enrichment) strategy combining protein-SELEX cycles on the recombinant α5β1 protein, surrounded by cell-SELEX cycles using two different cell lines. We identified aptamer H02, able to differentiate, in cyto- and histofluorescence assays, glioblastoma cell lines, and tissues from patient-derived tumor xenografts according to their α5 expression levels. Aptamer H02 is therefore an interesting tool for glioblastoma tumor characterization.

KEYWORDS:

SELEX; aptahistofluorescence; aptamer; cell-surface biomarker; cytofluorescence; glioblastoma; integrin α5β1; therapeutic payloads delivery

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