Exon 51 of human dystrophin pre-messenger RNA (DMD Exon 51) (DMD Exon 51)

Exon 51 of the human dystrophin pre-messenger RNA (pre-mRNA) is a specific genetic sequence within the DMD gene transcript that serves as a therapeutic target for antisense oligonucleotide (ASO) therapy. In patients with Duchenne muscular dystrophy (DMD), mutations often disrupt the translational reading frame, preventing the production of functional dystrophin protein, which is essential for muscle membrane integrity (UniProt: P11532). By targeting the exon 51 sequence, ASOs such as eteplirsen bind to the pre-mRNA and sterically block the splicing machinery from including this exon in the mature mRNA transcript (FDA: Exondys 51 Label). This "exon skipping" strategy restores the reading frame, allowing for the synthesis of an internally truncated but partially functional dystrophin protein, similar to that seen in the milder Becker muscular dystrophy (PubMed: 21784359). Successful engagement of this target is typically monitored by measuring the levels of exon 51-skipped mRNA and the subsequent expression of dystrophin protein in muscle biopsies (PubMed: 23902088). Clinical efficacy is also evaluated through functional assessments like the 6-minute walk test. This target is specific to the approximately 13% of DMD patients whose mutations are amenable to exon 51 skipping.

Other names

Dystrophin exon 51DMD exon 51Exon 51 of the DMD gene

Antisense oligonucleotides bind to the exon 51 sequence of the dystrophin pre-mRNA, sterically hindering the spliceosome to induce skipping of the exon and restore the reading frame (FDA: Exondys 51 Label).