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J. Pers. Med. 2017, 7(4), 13; https://doi.org/10.3390/jpm7040013

Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy

1
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, 8812-112 St., Edmonton, AB T6G 2H7, Canada
2
The Friends of Garret Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, 8812-112 St., Edmonton, AB T6G 2H7, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Stephen B. Liggett
Received: 22 September 2017 / Revised: 8 October 2017 / Accepted: 8 October 2017 / Published: 16 October 2017
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Abstract

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. View Full-Text
Keywords: 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 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
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Nguyen, Q.; Yokota, T. Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy. J. Pers. Med. 2017, 7, 13.

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