Zotadirsen

Zotadirsen is the core component of the AOC drug Delpacibart zotadirsen (AOC1044), consisting of a phosphorodiamidate morpholino oligonucleotide (PMO) targeting exon 44 of the dystrophin gene and an SMCC linker. Upon conjugation with the anti-TfR1 antibody Delpacibart, Zotadirsen exerts splicing regulatory activity and mediates exon skipping. Zotadirsen can be used in studies related to AOC synthesis ^{[1] [2]}.

In Vivo, Zotadirsen, which composes Delpacibart zotadirsen (AOC1044), can accumulate in muscle tissue to reach therapeutically effective concentrations^[1]. Zotadirsen, the active oligonucleotide component of Delpacibart zotadirsen (5–10 mg/kg), induces exon 44 skipping in a dose-dependent manner, elevates dystrophin expression in DMD44 subjects, reduces serum markers of muscle injury, and exhibits favorable safety and tolerability profiles^[2].

References:
[1]. Tang A, et al. Brogidirsen and Exon 44 Skipping for Duchenne Muscular Dystrophy: Advances and Challenges in RNA-Based Therapy. Genes. 2025 Jun 30;16(7):777.
[2]. Veerapandiyan A, et al. 674P Delpacibart zotadirsen (del-zota) increased dystrophin and improved muscle integrity markers regardless of ambulatory status in individuals with DMD44. Neuromuscular Disorders, 2025, 53(Supplement): 105650.