CRISPR-Cas9-Mediated Upregulation of Utrophin Ameliorates Duchenne Muscular Dystrophy - PubMed
5 hours ago
- #Duchenne Muscular Dystrophy
- #Gene Therapy
- #CRISPR-Cas9
- CRISPR-Cas9 was used to upregulate utrophin, a dystrophin paralogue, as a potential therapy for Duchenne muscular dystrophy (DMD).
- The strategy involved disrupting repressor binding sites, particularly the micro-RNA Let-7c binding site, to relieve repression of the UTRN gene.
- Cas9-generated indels were as effective as complete removal of the Let-7c binding site in upregulating UTRN expression, with minimal off-target effects.
- In a 3D tissue-engineered human skeletal muscle model of DMD, this editing strategy improved calcium regulation and muscle contraction.
- In mdx mice, local or systemic delivery of recombinant adeno-associated viruses encoding Cas9 and gRNA targeting the Let-7c site resulted in utrophin upregulation and improved muscle histopathology and function.
- This approach provides a mutation-independent, potentially universal gene editing therapeutic strategy for DMD.