Dystrophin pre-mRNA exon 51 exonic splicing enhancer (DMD exon 51 ESE)

The dystrophin pre-mRNA exon 51 exonic splicing enhancer is a regulatory sequence within the DMD gene transcript that promotes the inclusion of exon 51 during the splicing process [PubMed, PMID: 27747028]. In Duchenne muscular dystrophy (DMD), mutations often disrupt the reading frame, leading to a complete lack of functional dystrophin protein and severe muscle wasting. This ESE is a primary therapeutic target for antisense oligonucleotides (ASOs) designed to induce exon skipping. By binding to this enhancer, ASOs like eteplirsen prevent the splicing machinery from recognizing exon 51, causing it to be bypassed during mRNA maturation [FDA.gov; Muscular Dystrophy Association]. This restoration of the reading frame allows for the synthesis of a truncated but partially functional dystrophin protein, potentially slowing disease progression. This approach is specifically applicable to the approximately 13% of DMD patients with mutations amenable to exon 51 skipping [Sarepta Therapeutics].

Other names

DMD exon 51 splicing regulatory elementExon 51 ESEDystrophin exon 51DMD exon 51

Antisense oligonucleotides bind to the exonic splicing enhancer (ESE) via Watson-Crick base pairing, sterically blocking the binding of splicing assembly factors such as serine/arginine-rich (SR) proteins. This prevents the recognition of exon 51 by the spliceosome, resulting in its exclusion (skipping) from the mature mRNA transcript to restore the translational reading frame [Nature Reviews Drug Discovery, 2017; FDA.gov].