Eteplirsen (Exondys 51), Golodirsen (Vyondys 53), Casimersen (Amondys 45), Viltolarsen (Viltepso)
Duchenne muscular dystrophy (DMD) is a severe X-linked genetic disorder caused by mutations in the DMD gene, which encodes dystrophin — a protein essential for maintaining the structural integrity of muscle fibers. Without functional dystrophin, muscle cells are progressively damaged during normal use, leading to progressive muscle weakness that typically begins in early childhood. Most boys with DMD lose the ability to walk by their early teens, and the condition eventually affects cardiac and respiratory muscles.
The DMD gene is one of the largest in the human genome, spanning 2.4 million base pairs with 79 exons. Most disease-causing mutations are deletions of one or more exons that disrupt the reading frame, preventing production of any functional dystrophin protein. This is what makes DMD particularly amenable to antisense oligonucleotide therapy through a strategy called exon skipping.
Exon skipping uses short synthetic DNA strands (antisense oligonucleotides, or ASOs) to mask specific exons during pre-mRNA splicing. By skipping the exon adjacent to the deletion, the reading frame is restored, allowing the cell to produce a shorter but partially functional dystrophin protein — similar to the milder Becker muscular dystrophy phenotype. The concept is straightforward: if a deletion of exons 49–50 breaks the reading frame, skipping exon 51 restores it.
DMD has the most advanced ASO treatment landscape of any genetic disease. Four exon-skipping ASO drugs are FDA-approved: Eteplirsen (Exondys 51, approved 2016) targets exon 51 and is applicable to approximately 13% of DMD patients. Golodirsen (Vyondys 53, approved 2019) targets exon 53. Casimersen (Amondys 45, approved 2021) targets exon 45. Viltolarsen (Viltepso, approved 2020) also targets exon 53. Together, these drugs cover roughly 30% of DMD patients. All four use phosphorodiamidate morpholino oligomer (PMO) chemistry, delivered by intravenous infusion.
However, the majority of DMD patients have deletions that require skipping of different exons — exons not covered by any approved drug. There are 79 exons in the DMD gene, and deletions can occur at many different positions. A patient with a deletion of exons 3–7, for example, would need an exon 8 skipping ASO that does not exist as an approved drug. This is where personalized ASO design becomes critical.
Pequliar designs patient-specific exon-skipping ASOs for any DMD mutation. The platform identifies the optimal target site on the pre-mRNA, designs antisense sequences that promote efficient exon skipping, scores candidates for binding affinity and off-target safety, and delivers synthesis-ready sequences with full chemistry assignment. For DMD patients whose specific deletion is not covered by an approved drug, a personalized ASO can be designed and pursued through compassionate use or right-to-try pathways — following the same scientific principle behind the four approved drugs, but tailored to the individual patient's mutation.
Describe your mutation and get ranked, synthesis-ready ASO candidates in minutes. $399 per design.
Start a designPequliar is a computational research tool for informational purposes only. All sequences are computationally predicted candidates that have not been experimentally validated. Pequliar does not prescribe, recommend, or administer any compound. Independent validation by qualified professionals is required.