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

The dystrophin pre-mRNA exon 51 splicing enhancer is a regulatory sequence within the DMD gene transcript that promotes the inclusion of exon 51 during pre-mRNA splicing (FDA, 2016). In Duchenne muscular dystrophy (DMD) patients with specific deletions, the inclusion of exon 51 results in an out-of-frame mRNA transcript, leading to a complete lack of functional dystrophin protein (NIH, 2023). This target is specifically utilized by antisense oligonucleotides (ASOs) to induce exon skipping. By binding to this enhancer sequence, drugs like eteplirsen sterically block the spliceosome's access, causing exon 51 to be omitted from the final mRNA (PubChem, 2024). This intervention restores the reading frame, enabling the synthesis of a truncated but internally functional dystrophin protein, which can mitigate the severe muscle wasting characteristic of the disease (Nature Reviews Drug Discovery, 2011). The resulting protein is similar to the partially functional dystrophin found in patients with the milder Becker muscular dystrophy. This therapeutic approach represents a significant advancement in precision medicine for genetic neuromuscular disorders.

Other names

Exon 51 exonic splicing enhancerDMD exon 51 ESEDystrophin exon 51 splicing regulatory elementESE of DMD exon 51

Antisense oligonucleotide binding to the exonic splicing enhancer to sterically block the splicing machinery, resulting in the exclusion of exon 51 from the mature mRNA transcript (FDA, 2016).