Figure 2.

Antisense-mediated exon skipping rationale for DMD. (A) Patients with DMD have mutations which disrupt the open reading frame of the dystrophin pre-mRNA. In this example, exon 50 is deleted, creating an out-of-frame mRNA and leading to the synthesis of a truncated non-functional or unstable dystrophin (left panel). An antisense oligonucleotide directed against exon 51 can induce effective skipping of exon 51 and restore the open reading frame, therefore generating an internally deleted but partly functional dystrophin (right panel). (B) Multi exon-skipping rationale for DMD. The optimal skipping of exons 45–55 leading to the del45–55 artificial dystrophin could transform the DMD phenotype into the asymptomatic or mild BMD phenotype. This multiple exon skipping could theoretically rescue up to 63% of DMD patients with a deletion (126).