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Efficient prime editing in two-cell mouse embryos using PEmbryo

  • Rebecca P. Kim-Yip,
  • Ryan McNulty,
  • Bradley Joyce,
  • Antonio Mollica,
  • Peter J. Chen,
  • Purnima Ravisankar,
  • Benjamin K. Law,
  • David R. Liu,
  • Jared E. Toettcher,
  • Evgueni A. Ivakine,
  • Eszter Posfai,
  • Britt Adamson

摘要

Using transient inhibition of DNA mismatch repair during a permissive stage of development, we demonstrate highly efficient prime editing of mouse embryos with few unwanted, local byproducts (average 58% precise edit frequency, 0.5% on-target error frequency across 13 substitution edits at 8 sites), enabling same-generation phenotyping of founders. Whole-genome sequencing reveals that mismatch repair inhibition increases off-target indels at low-complexity regions in the genome without any obvious phenotype in mice.