Dystrophin (DMD) pre-mRNA exons 45–55 splice-regulatory regions (DMD exons 45–55)

The Dystrophin (DMD) pre-mRNA exons 45–55 splice-regulatory regions are critical sequences within the primary transcript of the DMD gene that govern the inclusion of these exons during mRNA processing [UniProt P11532]. This region is a major therapeutic target for Duchenne Muscular Dystrophy (DMD), a severe muscle-wasting disease caused by mutations that disrupt the dystrophin reading frame and prevent the production of functional protein. By using antisense oligonucleotides (ASOs) to mask these splice-regulatory elements, the splicing machinery can be redirected to skip specific exons, thereby restoring the reading frame and allowing for the production of a truncated but partially functional dystrophin protein [PubMed 28813521]. The 45–55 exon block is particularly significant because it represents a hotspot for deletions; skipping this entire region (multi-exon skipping) could potentially benefit approximately 13% of the DMD patient population [PubMed 33454514]. Several FDA-approved drugs, such as eteplirsen and casimersen, currently target individual exons within this range to treat specific mutation subgroups. Ongoing research into multi-exon skipping aims to target the broader 45–55 region to provide a more universal treatment for patients with various deletions in this area.

Other names

DMD pre-mRNA exons 45-55Dystrophin exons 45-55 splice sitesDMD multi-exon skipping targetDystrophin exons 45-55 exonic splicing enhancers

Antisense oligonucleotides (ASOs) bind to specific sequences such as exonic splicing enhancers (ESEs) within the pre-mRNA, sterically blocking the spliceosome's access and leading to the exclusion of targeted exons from the mature mRNA (exon skipping) [PubMed 28813521].