Dystrophin pre-mRNA exon 53 splice regulatory sequences (DMD exon 53)

Dystrophin pre-mRNA exon 53 splice regulatory sequences are specific nucleotide regions within the primary transcript of the DMD gene that facilitate the inclusion of exon 53 into the final messenger RNA. In patients with Duchenne muscular dystrophy (DMD) who have deletions of adjacent exons (such as exons 45-52 or 52), the reading frame is shifted, resulting in a premature stop codon and a lack of functional dystrophin protein (FDA, 2020). These regulatory sequences are the therapeutic target for antisense oligonucleotides (ASOs) like viltolarsen and golodirsen, which are designed to bind specifically to these sites (Heo, 2020). By binding to these sequences, the ASOs sterically block the splicing machinery, leading to the exclusion of exon 53 from the mature mRNA (Frank et al., 2020). This "exon skipping" restores the reading frame, allowing the cell to produce a truncated but partially functional dystrophin protein, which helps maintain muscle fiber stability. This therapeutic strategy aims to slow the progressive muscle degeneration characteristic of DMD in patients with amenable mutations. Monitoring efficacy typically involves measuring dystrophin protein levels in muscle biopsies and assessing exon skipping via RT-PCR (FDA, 2019).

Other names

DMD exon 53Dystrophin exon 53Exon 53 of the DMD gene

Antisense oligonucleotides bind to splice regulatory sequences to induce exon 53 skipping, restoring the mRNA reading frame.