Citation:
PLoS One. 2018 May 17;13(5):e0197084. doi: 10.1371/journal.pone.0197084. eCollection 2018
Abstract:
Antisense-mediated exon skipping has made significant progress as a therapeutic platform in recent years, especially in the case of Duchenne muscular dystrophy (DMD). Despite FDA approval of eteplirsen-the first-ever antisense drug clinically marketed for DMD-exon skipping therapy still faces the significant hurdles of limited applicability and unknown truncated protein function. In-frame exon skipping of dystrophin exons 45-55 represents a significant approach to treating DMD, as a large proportion of patients harbor mutations within this "hotspot" region. Additionally, patients harboring dystrophin exons 45-55 deletion mutations are reported to have exceptionally mild to asymptomatic phenotypes. Here, we demonstrate that a cocktail of phosphorodiamidate morpholino oligomers can effectively skip dystrophin exons 45-55 in vitro in myotubes transdifferentiated from DMD patient fibroblast cells. This is the first report of substantive exons 45-55 skipping in DMD patient cells. These findings help validate the use of transdifferentiated patient fibroblast cells as a suitable cell model for dystrophin exon skipping assays and further emphasize the feasibility of dystrophin exons 45-55 skipping in patients.
Epub:
Not Epub
Link to Publication:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197084
Organism or Cell Type:
cell culture: primary figroblasts differentiated to myotubes
Delivery Method:
Endo-Porter