Journal article
Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2 expressing tumors
Molecular therapy. Nucleic acids, Vol.32, pp.P758-772
05/2023
DOI: 10.1016/j.omtn.2023.05.003
PMCID: PMC10213179
PMID: 37251690
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.
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Santana-Viera and colleagues developed a novel 2’F-Py RNA aptamer against EphA2 receptor using a combinatorial SELEX strategy. Its anti-tumorigenic properties shown in vitro and in vivo, put forward this aptamer as a promising candidate for the development of aptamer-based therapeutics towards the many tumors over-expressing EphA2.
Details
- Title: Subtitle
- Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2 expressing tumors
- Creators
- Laura Santana-Viera - Institut d'Investigació Biomédica de BellvitgeJustin P. Dassie - University of IowaMarta Rosàs-Lapeña - Institut d'Investigació Biomédica de BellvitgeSilvia Garcia-Monclús - Institut d'Investigació Biomédica de BellvitgeMariona Chicón-Bosch - Institut d'Investigació Biomédica de BellvitgeMarina Pérez-Capó - Institut d'Investigació Biomédica de BellvitgeLidia del Pozo - Institut d'Investigació Biomédica de BellvitgeSara Sanchez-Serra - Institut d'Investigació Biomédica de BellvitgeOlga Almacellas-Rabaiget - Institut d'Investigació Biomédica de BellvitgeSusana Maqueda-Marcos - Institut d'Investigació Biomédica de BellvitgeRoser López-Alemany - Institut d'Investigació Biomédica de BellvitgeWilliam H. Thiel - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, Iowa, USAPaloma H. Giangrande - University of IowaOscar M. Tirado - Institut d'Investigació Biomédica de Bellvitge
- Resource Type
- Journal article
- Publication Details
- Molecular therapy. Nucleic acids, Vol.32, pp.P758-772
- DOI
- 10.1016/j.omtn.2023.05.003
- PMID
- 37251690
- PMCID
- PMC10213179
- NLM abbreviation
- Mol Ther Nucleic Acids
- ISSN
- 2162-2531
- eISSN
- 2162-2531
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 05/2023
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984413073802771
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