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Targeting fidelity of adenine and cytosine base editors in mouse embryos

Author

Listed:
  • Hye Kyung Lee

    (US National Institutes of Health)

  • Michaela Willi

    (US National Institutes of Health)

  • Shannon M. Miller

    (Broad Institute of MIT and Harvard
    Harvard University
    Harvard University)

  • Sojung Kim

    (US National Institutes of Health)

  • Chengyu Liu

    (Transgenic Core, National Heart, Lung, and Blood Institute, US National Institutes of Health)

  • David R. Liu

    (Broad Institute of MIT and Harvard
    Harvard University
    Harvard University)

  • Lothar Hennighausen

    (US National Institutes of Health)

Abstract

Base editing directly converts a target base pair into a different base pair in the genome of living cells without introducing double-stranded DNA breaks. While cytosine base editors (CBE) and adenine base editors (ABE) are used to install and correct point mutations in a wide range of organisms, the extent and distribution of off-target edits in mammalian embryos have not been studied in detail. We analyze on-target and proximal off-target editing at 13 loci by a variety of CBEs and ABE in more than 430 alleles generated from mouse zygotic injections using newly generated and published sequencing data. ABE predominantly generates anticipated A•T-to-G•C edits. Among CBEs, SaBE3 and BE4, result in the highest frequencies of anticipated C•G-to-T•A products relative to editing byproducts. Together, these findings highlight the remarkable fidelity of ABE in mouse embryos and identify preferred CBE variants when fidelity in vivo is critical.

Suggested Citation

  • Hye Kyung Lee & Michaela Willi & Shannon M. Miller & Sojung Kim & Chengyu Liu & David R. Liu & Lothar Hennighausen, 2018. "Targeting fidelity of adenine and cytosine base editors in mouse embryos," Nature Communications, Nature, vol. 9(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07322-7
    DOI: 10.1038/s41467-018-07322-7
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