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

The Dystrophin (DMD) pre-mRNA exon 53 splice-regulatory sequence is a critical segment of the primary transcript of the DMD gene, which encodes the dystrophin protein essential for maintaining muscle fiber integrity (UniProt P11532). In a specific subset of patients with Duchenne muscular dystrophy (DMD), genetic deletions result in an out-of-frame mRNA transcript, leading to a premature stop codon and a total absence of functional dystrophin. This splice-regulatory sequence serves as the therapeutic target for antisense oligonucleotides (ASOs) designed to induce "exon skipping." By binding to this sequence, drugs like golodirsen (Vyondys 53) and viltolarsen (Viltepso) sterically block the splicing machinery, causing exon 53 to be excluded from the mature mRNA (FDA Label: Vyondys 53; FDA Label: Viltepso). This process restores the reading frame, enabling the production of a truncated but partially functional dystrophin protein, similar to that found in the milder Becker muscular dystrophy. The therapeutic goal is to slow the progression of muscle weakness and preserve motor function in patients amenable to exon 53 skipping.

Other names

DMD exon 53Dystrophin exon 53DMD pre-mRNA exon 53Exon 53 of the DMD gene

Antisense oligonucleotides bind to the exon 53 splice-regulatory sequence of the DMD pre-mRNA, sterically hindering the spliceosome to induce exon skipping and restore the mRNA reading frame.