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

doi:10.1038/s41587-023-02106-x

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

Princeton University

Research output: Contribution to journal › Article › peer-review

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.

Original language	American English
Article number	5855
Pages (from-to)	1822-1830
Number of pages	9
Journal	Nature biotechnology
Volume	42
Issue number	12
DOIs	https://doi.org/10.1038/s41587-023-02106-x
State	Published - Dec 2024

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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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.",

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doi = "10.1038/s41587-023-02106-x",

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AU - Kim-Yip, Rebecca P.

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AU - Mollica, Antonio

AU - Chen, Peter J.

AU - Ravisankar, Purnima

AU - Law, Benjamin K.

AU - Liu, David R.

AU - Toettcher, Jared E.

AU - Ivakine, Evgueni A.

AU - Posfai, Eszter

AU - Adamson, Britt

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AB - 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.

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Efficient prime editing in two-cell mouse embryos using PEmbryo

Abstract

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