Dystrophin pre-messenger RNA exon 53 (DMD exon 53)

The exon 53 region of the dystrophin (DMD) pre-mRNA is a critical therapeutic target for a subset of patients with Duchenne muscular dystrophy (DMD), a progressive neuromuscular disorder caused by mutations in the DMD gene (Source: NIH/GARD). In patients amenable to exon 53 skipping, specific deletions disrupt the mRNA reading frame, preventing the production of functional dystrophin protein, which normally stabilizes muscle fibers during contraction (Source: StatPearls). Antisense oligonucleotides (ASOs) are designed to bind specifically to the exon 53 sequence within the pre-mRNA, masking it from the spliceosome (Source: PubMed PMC6933533). This results in the exclusion of exon 53 from the mature mRNA, restoring the reading frame and enabling the synthesis of a truncated but functional dystrophin protein, similar to that found in the milder Becker muscular dystrophy (Source: FDA). Drugs such as viltolarsen and golodirsen utilize this mechanism to increase dystrophin levels in muscle tissue (Source: FDA). Clinical monitoring involves assessing dystrophin expression via muscle biopsy and monitoring for potential renal toxicity, a risk associated with this class of drugs (Source: Vyondys 53 and Viltepso Prescribing Information).

Other names

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

Antisense oligonucleotide-mediated exon skipping to restore the mRNA reading frame