Dystrophin (DMD) pre-mRNA exon 8 splicing regulatory region

The Dystrophin (DMD) pre-mRNA exon 8 splicing regulatory region is a sequence-specific target within the primary transcript of the DMD gene that governs the inclusion of exon 8 into the mature mRNA [1]. This region contains exonic splicing enhancers (ESEs) that are recognized by serine/arginine-rich (SR) proteins to promote spliceosome assembly and exon recognition [2]. In therapeutic contexts, this region is targeted by antisense oligonucleotides (ASOs) to induce "exon skipping," a process that bypasses exon 8 during splicing to restore the translational reading frame in patients with specific mutations, such as deletions of exon 7 or exons 3-7 [3]. By sterically blocking the regulatory elements, ASOs prevent the splicing machinery from recognizing the exon, leading to its exclusion from the final mRNA transcript [4]. This strategy aims to produce a truncated but partially functional dystrophin protein, potentially converting a severe Duchenne muscular dystrophy (DMD) phenotype into a milder Becker muscular dystrophy (BMD) phenotype [2]. While clinical development has historically prioritized more common exons like 51 and 53, the exon 8 regulatory region remains a vital target for personalized genetic medicine in DMD [3].

Other names

DMD exon 8 exonic splicing enhancerDMD exon 8 ESEDystrophin exon 8 splicing regionDMD exon 8 splicing regulatory element

Antisense oligonucleotide-mediated exon skipping via steric hindrance of splicing regulatory elements