Background of exon skipping
Over the last 10 to 15 years much effort has been put into the development of a safe and efficient gene therapy for DMD. However, the DMD gene and its product initially seemed too large and too complex to allow a straightforward approach. Over the last few years an innovative tool has emerged with which an escape route can be utilized that nature had already hinted at. Some DMD patients have rare, dystrophin-positive fibres (“revertant fibers”), originating from reading frame-restoring exon skipping. Several laboratories have recently shown that we can actually enhance or induce this therapeutic exon skipping using small synthetic antisense oligoribonucleotides, the so called AONs. Through inducing the skipping of exons during the splicing, AONs can restore the reading-frame of the dystrophin transcript (mRNA), and thus convert DMD into BMD-like fibers.