Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy

Seuk Min Ryu, Taeyoung Koo, Kyoungmi Kim, Kayeong Lim, Gayoung Baek, Sang Tae Kim, Heon Seok Kim, Da Eun Kim, Hyunji Lee, Eugene Chung, Jin Soo Kim

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60 Citations (Scopus)

Abstract

Adenine base editors (ABEs) composed of an engineered adenine deaminase and the Streptococcus pyogenes Cas9 nickase enable adenine-to-guanine (A-to-G) single-nucleotide substitutions in a guide RNA (gRNA)-dependent manner. Here we demonstrate application of this technology in mouse embryos and adult mice. We also show that long gRNAs enable adenine editing at positions one or two bases upstream of the window that is accessible with standard single guide RNAs (sgRNAs). We introduced the Himalayan point mutation in the Tyr gene by microinjecting ABE mRNA and an extended gRNA into mouse embryos, obtaining Tyr mutant mice with an albino phenotype. Furthermore, we delivered the split ABE gene, using trans-splicing adeno-associated viral vectors, to muscle cells in a mouse model of Duchenne muscular dystrophy to correct a nonsense mutation in the Dmd gene, demonstrating the therapeutic potential of base editing in adult animals.

Original languageEnglish
Pages (from-to)536-539
Number of pages4
JournalNature Biotechnology
Volume36
Issue number6
DOIs
Publication statusPublished - 2018 Jul 1

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ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

Cite this

Ryu, S. M., Koo, T., Kim, K., Lim, K., Baek, G., Kim, S. T., Kim, H. S., Kim, D. E., Lee, H., Chung, E., & Kim, J. S. (2018). Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy. Nature Biotechnology, 36(6), 536-539. https://doi.org/10.1038/nbt.4148