AOC 1044 induces exon 44 skipping and restores dystrophin protein in preclinical models of Duchenne muscular dystrophy.

ABSTRACT: Duchenne muscular dystrophy (DMD) is a severe disorder caused by mutations in the dystrophin gene, resulting in loss of functional dystrophin protein in muscle. While phosphorodiamidate morpholino oligomers (PMOs) are promising exon-skipping therapeutics aimed at restoring dystrophin expression, their effectiveness is often limited by poor muscle delivery. We developed AOC 1044, an antibody-oligonucleotide conjugate (AOC) that combines a PMO-targeting exon 44 with an antibody against the transferrin receptor (TfR1), enhancing delivery to muscle tissues for patients with DMD amenable to exon 44 skipping (DMD44). AOC 1044 induces dose-dependent exon 44 skipping and its mouse-active variant elicited dose-dependent dystrophin restoration in skeletal and cardiac muscle in a DMD mouse model. Thi

SUBMITTER: Etxaniz U 

PROVIDER: S-EPMC11969676 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature