Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD) gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs) is one of the most promising strategies....
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MDPI AG
2017-10-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/7/4/13 |
| _version_ | 1797761603463020544 |
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| author | Quynh Nguyen Toshifumi Yokota |
| author_facet | Quynh Nguyen Toshifumi Yokota |
| author_sort | Quynh Nguyen |
| collection | DOAJ |
| description | Duchenne muscular dystrophy (DMD) is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD) gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs) is one of the most promising strategies. This strategy aims to restore the reading frame, thus producing a truncated, yet functioning dystrophin protein. In 2016, the Food and Drug Administration (FDA) conditionally approved the first AO-based drug, eteplirsen (Exondys 51), developed for DMD exon 51 skipping. An accurate and reproducible method to quantify exon skipping efficacy is essential for evaluating the therapeutic potential of different AOs sequences. However, previous in vitro screening studies have been hampered by the limited proliferative capacity and insufficient amounts of dystrophin expressed by primary muscle cell lines that have been the main system used to evaluate AOs sequences. In this paper, we illustrate the challenges associated with primary muscle cell lines and describe a novel approach that utilizes immortalized cell lines to quantitatively evaluate the exon skipping efficacy in in vitro studies. |
| first_indexed | 2024-03-12T19:15:24Z |
| format | Article |
| id | doaj.art-c5fa885e4ae548e3b4b67fa173163a20 |
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| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-12T19:15:24Z |
| publishDate | 2017-10-01 |
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| series | Journal of Personalized Medicine |
| spelling | doaj.art-c5fa885e4ae548e3b4b67fa173163a202023-08-02T05:35:09ZengMDPI AGJournal of Personalized Medicine2075-44262017-10-01741310.3390/jpm7040013jpm7040013Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular DystrophyQuynh Nguyen0Toshifumi Yokota1Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, 8812-112 St., Edmonton, AB T6G 2H7, CanadaDepartment of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, 8812-112 St., Edmonton, AB T6G 2H7, CanadaDuchenne muscular dystrophy (DMD) is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD) gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs) is one of the most promising strategies. This strategy aims to restore the reading frame, thus producing a truncated, yet functioning dystrophin protein. In 2016, the Food and Drug Administration (FDA) conditionally approved the first AO-based drug, eteplirsen (Exondys 51), developed for DMD exon 51 skipping. An accurate and reproducible method to quantify exon skipping efficacy is essential for evaluating the therapeutic potential of different AOs sequences. However, previous in vitro screening studies have been hampered by the limited proliferative capacity and insufficient amounts of dystrophin expressed by primary muscle cell lines that have been the main system used to evaluate AOs sequences. In this paper, we illustrate the challenges associated with primary muscle cell lines and describe a novel approach that utilizes immortalized cell lines to quantitatively evaluate the exon skipping efficacy in in vitro studies.https://www.mdpi.com/2075-4426/7/4/13Duchenne/Becker muscular dystrophy (DMD/BMD)antisense oligonucleotide-mediated exon skipping therapyhDMD micehuman telomerase reverse transcriptase (hTERT)cyclin-dependent-kinase 4 (Cdk4)phosphorodiamidate morpholino oligomers (PMOs or morpholinos)C2C12dystrophin-glycoprotein complex (DGC)golodirsen (SRP-4053)NS-065/NCNP-01 |
| spellingShingle | Quynh Nguyen Toshifumi Yokota Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy Journal of Personalized Medicine Duchenne/Becker muscular dystrophy (DMD/BMD) antisense oligonucleotide-mediated exon skipping therapy hDMD mice human telomerase reverse transcriptase (hTERT) cyclin-dependent-kinase 4 (Cdk4) phosphorodiamidate morpholino oligomers (PMOs or morpholinos) C2C12 dystrophin-glycoprotein complex (DGC) golodirsen (SRP-4053) NS-065/NCNP-01 |
| title | Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy |
| title_full | Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy |
| title_fullStr | Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy |
| title_full_unstemmed | Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy |
| title_short | Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy |
| title_sort | immortalized muscle cell model to test the exon skipping efficacy for duchenne muscular dystrophy |
| topic | Duchenne/Becker muscular dystrophy (DMD/BMD) antisense oligonucleotide-mediated exon skipping therapy hDMD mice human telomerase reverse transcriptase (hTERT) cyclin-dependent-kinase 4 (Cdk4) phosphorodiamidate morpholino oligomers (PMOs or morpholinos) C2C12 dystrophin-glycoprotein complex (DGC) golodirsen (SRP-4053) NS-065/NCNP-01 |
| url | https://www.mdpi.com/2075-4426/7/4/13 |
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