# Efficient precise in vivo base editing in adult dystrophic mice

Article · Xu L, Zhang C, Li H, Wang P, Gao Y, Mokadam NA, Ma J, Arnold WD, Han R

- Archive id: doi:10.1038/s41467-021-23996-y
- Published: 2021-06-17
- Venue: Nature communications
- DOI: https://doi.org/10.1038/s41467-021-23996-y
- PMID: 34140489
- PMCID: PMC8211797
- Citations: 100
- Source URL: https://doi.org/10.1038/s41467-021-23996-y
- PDF: https://europepmc.org/articles/PMC8211797/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [CRISPR & Gene-Editing Therapies](https://space-kitty.com/topics/gene-editing-therapies)

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