Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers
Oligonucleotide gene therapy has shown great promise for the treatment of muscular dystrophies. Nevertheless, the selective delivery to affected muscles has shown to be challenging because of their high representation in the body and the high complexity of their cell membranes. Current trials show l...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253117303025 |
| _version_ | 1818508255618400256 |
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| author | Styliana Philippou Nikolaos P. Mastroyiannopoulos Neoklis Makrides Carsten W. Lederer Marina Kleanthous Leonidas A. Phylactou |
| author_facet | Styliana Philippou Nikolaos P. Mastroyiannopoulos Neoklis Makrides Carsten W. Lederer Marina Kleanthous Leonidas A. Phylactou |
| author_sort | Styliana Philippou |
| collection | DOAJ |
| description | Oligonucleotide gene therapy has shown great promise for the treatment of muscular dystrophies. Nevertheless, the selective delivery to affected muscles has shown to be challenging because of their high representation in the body and the high complexity of their cell membranes. Current trials show loss of therapeutic molecules to non-target tissues leading to lower target efficacy. Therefore, strategies that increase uptake efficiency would be particularly compelling. To address this need, we applied a cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment) approach and identified a skeletal muscle-specific RNA aptamer. A01B RNA aptamer preferentially internalizes in skeletal muscle cells and exhibits decreased affinity for off-target cells. Moreover, this in vitro selected aptamer retained its functionality in vivo, suggesting a potential new approach for targeting skeletal muscles. Ultimately, this will aid in the development of targeted oligonucleotide therapies against muscular dystrophies. |
| first_indexed | 2024-12-10T22:29:08Z |
| format | Article |
| id | doaj.art-6e90ec69d69243b4a73ae36a11dd9eab |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-10T22:29:08Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-6e90ec69d69243b4a73ae36a11dd9eab2022-12-22T01:31:05ZengElsevierMolecular Therapy: Nucleic Acids2162-25312018-03-011019921410.1016/j.omtn.2017.12.004Selection and Identification of Skeletal-Muscle-Targeted RNA AptamersStyliana Philippou0Nikolaos P. Mastroyiannopoulos1Neoklis Makrides2Carsten W. Lederer3Marina Kleanthous4Leonidas A. Phylactou5Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, CyprusDepartment of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, CyprusClinic A, Neuropathology Department, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, CyprusDepartment of Molecular Genetics Thalassaemia, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, CyprusDepartment of Molecular Genetics Thalassaemia, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, CyprusDepartment of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus; Corresponding author: Leonidas A. Phylactou, PhD, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.Oligonucleotide gene therapy has shown great promise for the treatment of muscular dystrophies. Nevertheless, the selective delivery to affected muscles has shown to be challenging because of their high representation in the body and the high complexity of their cell membranes. Current trials show loss of therapeutic molecules to non-target tissues leading to lower target efficacy. Therefore, strategies that increase uptake efficiency would be particularly compelling. To address this need, we applied a cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment) approach and identified a skeletal muscle-specific RNA aptamer. A01B RNA aptamer preferentially internalizes in skeletal muscle cells and exhibits decreased affinity for off-target cells. Moreover, this in vitro selected aptamer retained its functionality in vivo, suggesting a potential new approach for targeting skeletal muscles. Ultimately, this will aid in the development of targeted oligonucleotide therapies against muscular dystrophies.http://www.sciencedirect.com/science/article/pii/S2162253117303025aptamerSELEXskeletal muscledeliverymuscular dystrophiesgene therapy |
| spellingShingle | Styliana Philippou Nikolaos P. Mastroyiannopoulos Neoklis Makrides Carsten W. Lederer Marina Kleanthous Leonidas A. Phylactou Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers Molecular Therapy: Nucleic Acids aptamer SELEX skeletal muscle delivery muscular dystrophies gene therapy |
| title | Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers |
| title_full | Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers |
| title_fullStr | Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers |
| title_full_unstemmed | Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers |
| title_short | Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers |
| title_sort | selection and identification of skeletal muscle targeted rna aptamers |
| topic | aptamer SELEX skeletal muscle delivery muscular dystrophies gene therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2162253117303025 |
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