Targeting Insulin Receptor with a Novel Internalizing Aptamer
Nucleic acid-based aptamers are emerging as therapeutic antagonists of disease-associated proteins such as receptor tyrosine kinases. They are selected by an in vitro combinatorial chemistry approach, named Systematic Evolution of Ligands by Exponential enrichment (SELEX), and thanks to their small...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253117300914 |
| _version_ | 1828432905029812224 |
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| author | Margherita Iaboni Raffaela Fontanella Anna Rienzo Maria Capuozzo Silvia Nuzzo Gianluca Santamaria Silvia Catuogno Gerolama Condorelli Vittorio de Franciscis Carla Lucia Esposito |
| author_facet | Margherita Iaboni Raffaela Fontanella Anna Rienzo Maria Capuozzo Silvia Nuzzo Gianluca Santamaria Silvia Catuogno Gerolama Condorelli Vittorio de Franciscis Carla Lucia Esposito |
| author_sort | Margherita Iaboni |
| collection | DOAJ |
| description | Nucleic acid-based aptamers are emerging as therapeutic antagonists of disease-associated proteins such as receptor tyrosine kinases. They are selected by an in vitro combinatorial chemistry approach, named Systematic Evolution of Ligands by Exponential enrichment (SELEX), and thanks to their small size and unique chemical characteristics, they possess several advantages over antibodies as diagnostics and therapeutics. In addition, aptamers that rapidly internalize into target cells hold as well great potential for their in vivo use as delivery tools of secondary therapeutic agents. Here, we describe a nuclease resistant RNA aptamer, named GL56, which specifically recognizes the insulin receptor (IR). Isolated by a cell-based SELEX method that allows enrichment for internalizing aptamers, GL56 rapidly internalizes into target cells and is able to discriminate IR from the highly homologous insulin-like growth factor receptor 1. Notably, when applied to IR expressing cancer cells, the aptamer inhibits IR dependent signaling. Given the growing interest in the insulin receptor as target for cancer treatment, GL56 reveals a novel molecule with great translational potential as inhibitor and delivery tool for IR-dependent cancers. |
| first_indexed | 2024-12-10T18:27:30Z |
| format | Article |
| id | doaj.art-53896330bbcb4b8ca34e6da81ae74ff0 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-10T18:27:30Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-53896330bbcb4b8ca34e6da81ae74ff02022-12-22T01:38:02ZengElsevierMolecular Therapy: Nucleic Acids2162-25312016-01-015C10.1038/mtna.2016.73Targeting Insulin Receptor with a Novel Internalizing AptamerMargherita Iaboni0Raffaela Fontanella1Anna Rienzo2Maria Capuozzo3Silvia Nuzzo4Gianluca Santamaria5Silvia Catuogno6Gerolama Condorelli7Vittorio de Franciscis8Carla Lucia Esposito9Department of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, ItalyIBB, CNR, Naples, ItalyIEOS, CNR, Naples, ItalyIEOS, CNR, Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, ItalyResearch Center of Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, ItalyIEOS, CNR, Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, ItalyIEOS, CNR, Naples, ItalyIEOS, CNR, Naples, ItalyNucleic acid-based aptamers are emerging as therapeutic antagonists of disease-associated proteins such as receptor tyrosine kinases. They are selected by an in vitro combinatorial chemistry approach, named Systematic Evolution of Ligands by Exponential enrichment (SELEX), and thanks to their small size and unique chemical characteristics, they possess several advantages over antibodies as diagnostics and therapeutics. In addition, aptamers that rapidly internalize into target cells hold as well great potential for their in vivo use as delivery tools of secondary therapeutic agents. Here, we describe a nuclease resistant RNA aptamer, named GL56, which specifically recognizes the insulin receptor (IR). Isolated by a cell-based SELEX method that allows enrichment for internalizing aptamers, GL56 rapidly internalizes into target cells and is able to discriminate IR from the highly homologous insulin-like growth factor receptor 1. Notably, when applied to IR expressing cancer cells, the aptamer inhibits IR dependent signaling. Given the growing interest in the insulin receptor as target for cancer treatment, GL56 reveals a novel molecule with great translational potential as inhibitor and delivery tool for IR-dependent cancers.http://www.sciencedirect.com/science/article/pii/S2162253117300914aptamercancer therapyIGF-1RIRSELEX |
| spellingShingle | Margherita Iaboni Raffaela Fontanella Anna Rienzo Maria Capuozzo Silvia Nuzzo Gianluca Santamaria Silvia Catuogno Gerolama Condorelli Vittorio de Franciscis Carla Lucia Esposito Targeting Insulin Receptor with a Novel Internalizing Aptamer Molecular Therapy: Nucleic Acids aptamer cancer therapy IGF-1R IR SELEX |
| title | Targeting Insulin Receptor with a Novel Internalizing Aptamer |
| title_full | Targeting Insulin Receptor with a Novel Internalizing Aptamer |
| title_fullStr | Targeting Insulin Receptor with a Novel Internalizing Aptamer |
| title_full_unstemmed | Targeting Insulin Receptor with a Novel Internalizing Aptamer |
| title_short | Targeting Insulin Receptor with a Novel Internalizing Aptamer |
| title_sort | targeting insulin receptor with a novel internalizing aptamer |
| topic | aptamer cancer therapy IGF-1R IR SELEX |
| url | http://www.sciencedirect.com/science/article/pii/S2162253117300914 |
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