{"id":"doi:10.1038/s41467-021-23996-y","kind":"article","title":"Efficient precise in vivo base editing in adult dystrophic mice","authors":["Xu L","Zhang C","Li H","Wang P","Gao Y","Mokadam NA","Ma J","Arnold WD","Han R"],"author_count":9,"year":2021,"published":"2021-06-17","venue":"Nature communications","cited_by":100,"doi":"10.1038/s41467-021-23996-y","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-021-23996-y","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-021-23996-y","updated":null,"pmid":"34140489","pmcid":"PMC8211797","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8211797/pdf","abstract":"Recent advances in base editing have created an exciting opportunity to precisely correct disease-causing mutations. However, the large size of base editors and their inherited off-target activities pose challenges for in vivo base editing. Moreover, the requirement of a protospacer adjacent motif (PAM) nearby the mutation site further limits the targeting feasibility. Here we modify the NG-targeting adenine base editor (iABE-NGA) to overcome these challenges and demonstrate the high efficiency to precisely edit a Duchenne muscular dystrophy (DMD) mutation in adult mice. Systemic delivery of AAV9-iABE-NGA results in dystrophin restoration and functional improvement. At 10 months after AAV9-iABE-NGA treatment, a near complete rescue of dystrophin is measured in mdx 4cv mouse hearts with up to 15% rescue in skeletal muscle fibers. The off-target activities remains low and no obvious toxicity is detected. This study highlights the promise of permanent base editing using iABE-NGA for the treatment of monogenic diseases.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Efficient precise in vivo base editing in adult dystrophic mice\" by Xu L, Zhang C, Li H et al., https://doi.org/10.1038/s41467-021-23996-y, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-editing-therapies","name":"CRISPR & Gene-Editing Therapies","domain_slug":"medicine"}],"cited_in_dossiers":[]}