Dystrophin pre-mRNA exon 6, 7, and 8 splice regulatory sequences (DMD pre-mRNA (Exons 6-8))

The target consists of the specific nucleotide sequences within exons 6, 7, and 8 of the Dystrophin (DMD) pre-mRNA that regulate the splicing process, including exonic splicing enhancers (ESEs) and splice donor/acceptor sites (PubMed: 29653608). In patients with Duchenne Muscular Dystrophy (DMD), mutations such as deletions in the DMD gene disrupt the open reading frame, leading to a complete lack of functional dystrophin protein, which is essential for muscle fiber integrity (NIH: GARD). By targeting these regulatory sequences with antisense oligonucleotides (ASOs), the splicing machinery can be redirected to skip the targeted exon(s) during mRNA processing (PubMed: 31433440). This strategy aims to restore the reading frame, allowing for the production of a truncated but partially functional dystrophin protein, similar to that found in the milder Becker Muscular Dystrophy (BMD). While drugs targeting exons 51, 53, and 45 are currently approved, sequences in exons 6, 7, and 8 represent critical targets for patients with specific proximal deletions, such as those involving exon 7 or exon 9, where skipping exon 8 can restore the frame (Pippin Genetics).

Other names

DMD exon 6-8 splice sitesDystrophin pre-mRNA regulatory elementsExonic splicing enhancers of DMD exons 6-8

Antisense oligonucleotide-mediated exon skipping