AON-C12

AON-C12 is an experimental antisense oligonucleotide (ASO) developed for the treatment of Duchenne muscular dystrophy (DMD). It is a phosphorothioate (PS) 18-mer composed of locked nucleic acids (LNAs), 2'-O-methyl (2'OMe), and 5-methyl-2'OMe-C-RNA nucleosides. The drug is designed to bind to a specific splicing enhancer site within exon 51 of the dystrophin (DMD) pre-mRNA, inducing exon skipping to restore the open reading frame. This mechanism allows for the production of an internally deleted but functional dystrophin protein, which aims to convert a severe DMD phenotype into a milder Becker muscular dystrophy (BMD) phenotype. AON-C12 served as the lead optimization precursor for BMN 351, a clinical candidate that incorporates an additional 5' triethylene glycol (TEG) modification to enhance safety and durability.