FocusDuchenne Muscular Dystrophy

Exon-Skipping Therapy: A Roadblock, Detour, or Bump in the Road?

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Science Translational Medicine  02 Apr 2014:
Vol. 6, Issue 230, pp. 230fs14
DOI: 10.1126/scitranslmed.3008873


  • Fig. 1 Repairing disrupted dystrophin.

    In exon-skipping therapy, DMD patients are treated systemically with antisense oligonucleotides (Oligo, reddish-brown bars) directed against the dystrophin mRNA transcript (exons 47 to 52 of the dystrophin gene are shown in purple inset). These oligos rescue the target mRNA (also shown in purple inset), restoring the proper reading frame and thus production of dystrophin protein (blue twisted structure). Dystrophin rescue is accomplished by excluding an exon that neighbors a deletion mutation (illustrated by [ ] in the dystrophin protein shown in the “After exon skipping” panel), effectively transforming an out-of-frame (nonsense, loss-of-function) transcript to an in-frame transcript capable of de novo dystrophin production in patient muscle. This dystrophin protein lacks some amino acids but retains cytoskeletal function. The dark red square in the muscle myofiber is amplified in three insets (at the left, outlined in dark red) that represent normal muscle (Normal), untreated Duchenne muscle (Duchenne), and Duchenne muscle after exon-skipping treatment (After exon skipping).


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