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

• Published in: Molecular therapy. Nucleic acids Vol. 17; pp. 63 - 77
• Main Authors: Fechter, Pierre, Cruz Da Silva, Elisabete, Mercier, Marie-Cécile, Noulet, Fanny, Etienne-Seloum, Nelly, Guenot, Dominique, Lehmann, Maxime, Vauchelles, Romain, Martin, Sophie, Lelong-Rebel, Isabelle, Ray, Anne-Marie, Seguin, Cendrine, Dontenwill, Monique, Choulier, Laurence
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06-09-2019; Elsevier Limited; Elsevier; American Society of Gene & Cell Therapy
• Subjects: Angiogenesis; aptahistofluorescence; aptamer; Aptamers; Biomarkers; Brain cancer; Cancer therapies; Cell adhesion & migration; Cell surface; cell-surface biomarker; Chemical modification; Chemotherapy; Cycle protein; cytofluorescence; DNA probes; Glioblastoma; Immunogenicity; integrin α5β1; Life Sciences; Ligands; Phenotypes; Proteins; Ribonucleic acid; RNA; SELEX; Solid tumors; Therapeutic applications; therapeutic payloads delivery; Toxicity; Xenografts; aptahistofluorescence; therapeutic payloads delivery; glioblastoma; aptamer; cytofluorescence; integrin α5β1; cell-surface biomarker; SELEX
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2019.05.006

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.
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