Dystrophin pre-messenger RNA exon 51 (DMD exon 51)

Dystrophin pre-messenger RNA (pre-mRNA) exon 51 is a specific genomic segment within the DMD gene transcript that serves as a therapeutic target for antisense oligonucleotide (ASO) therapies in Duchenne muscular dystrophy (DMD) [1, 5]. DMD is a fatal X-linked neuromuscular disorder caused by mutations—most commonly deletions—that disrupt the translational reading frame of the DMD gene, resulting in a lack of functional dystrophin protein [3, 8]. Dystrophin is essential for maintaining the structural integrity of muscle fibers by linking the cytoskeleton to the extracellular matrix [1, 12]. Exon 51 is a strategic target because skipping this specific exon can restore the reading frame for approximately 13-14% of DMD patients, the largest single subgroup amenable to this approach [5, 13]. Therapeutic agents like Eteplirsen (Exondys 51) bind to the exon 51 sequence in the pre-mRNA, masking it from the splicing machinery and causing it to be excluded from the mature mRNA [1, 6]. This exon skipping results in the production of an internally truncated but partially functional dystrophin protein, potentially converting a severe DMD phenotype into a milder Becker-like phenotype [3, 14]. While Eteplirsen was the first to receive accelerated approval, challenges remain regarding the efficiency of dystrophin restoration and delivery to muscle tissues [14, 16]. Recent developments have explored next-generation ASOs, such as peptide-conjugated morpholinos (e.g., Vesleteplirsen), though some have faced safety hurdles like hypomagnesemia and renal concerns [11, 15].

Other names

DMD exon 51Dystrophin exon 51Exon 51 of the DMD geneDystrophin pre-mRNA exon 51

Antisense oligonucleotide-mediated exon skipping to restore the translational reading frame of the DMD transcript.