Long-term reversal of Duchenne muscular dystrophy via circular arRNA-guided exon skipping in monkeys and humans - PubMed
3 hours ago
- #exon skipping
- #RNA editing
- #DMD therapy
- The study uses an RNA editing platform, LEAPER 2.0, to achieve exon skipping in Duchenne muscular dystrophy (DMD) via circular ADAR-recruiting RNAs (circ-arRNAs), both in monkeys and humans.
- In nonhuman primates with DMD mutations, a single dose led to long-term dystrophin restoration and motor improvement for over 1.5 years, without triggering immune responses against dystrophin.
- In a first-in-human trial, a single AAV-delivered circ-arRNA dose safely produced dose-dependent exon skipping, with measurable improvements in motor and cardiopulmonary functions in patients.
- The approach works by hijacking endogenous ADAR and splicing mechanisms to bypass out-of-frame DMD mutations, restoring dystrophin through both ADAR-dependent and independent pathways.
- Results across models and patients demonstrate the translational potential of circ-arRNA-mediated exon skipping as a durable therapeutic strategy for DMD.