Efficient prime editing in two-cell mouse embryos using PEmbryo.

Kim-Yip, Rebecca P; McNulty, Ryan; Joyce, Bradley; Mollica, Antonio; Chen, Peter J; Ravisankar, Purnima; Law, Benjamin K; Liu, David R et al. · Nat Biotechnol · 2024

basic_science · Level V

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Abstract

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.

Medical subject headings