Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2-expressing tumors
Laura Santana-Viera, Justin P. Dassie, Marta Rosàs‐Lapeña, Sílvia García-Monclús, Mariona Chicón‐Bosch, Marina Pérez-Capó, Lidia del Pozo, Sara Sánchez‐Serra, Olga Almacellas‐Rabaiget, Susana Maqueda-Marcos, Roser López‐Alemany, William H. Thiel, Paloma H. Giangrande, Òscar M. Tirado
Abstract
The EphA2 receptor tyrosine kinase is overexpressed in most solid tumors and acts as the major driver of tumorigenesis. In this study, we developed a novel approach for targeting the EphA2 receptor using a 2'-fluoro-modified pyrimidine RNA aptamer termed ATOP. We identified the ATOP EphA2 aptamer using a novel bioinformatics strategy that compared aptamers enriched during a protein SELEX using recombinant human EphA2 and a cell-internalization SELEX using EphA2-expressing MDA231 tumor cells. When applied to EphA2-expressing tumor cell lines, the ATOP EphA2 aptamer attenuated tumor cell migration and clonogenicity. In a mouse model of spontaneous metastasis, the ATOP EphA2 aptamer slowed primary tumor growth and significantly reduced the number of lung metastases. The EphA2 ATOP aptamer represents a promising candidate for the development of next-generation targeted therapies that provide safer and more effective treatment of EphA2-overexpressing tumors.