Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

Genome Biol. 2019 May 22;20(1):101. doi: 10.1186/s13059-019-1703-6.

Abstract

Base editing installs a precise nucleotide change in specific gene loci without causing a double-strand break. Its efficiency in human embryos is generally low, limiting its utility in functional genetic studies. Here, we report that injecting base editors into human cleaving two-cell and four-cell embryos results in much higher (up to 13-fold) homozygotic nucleotide substitution efficiency as opposed to MII oocytes or zygotes. Furthermore, as a proof-of-principle study, a point mutation can be efficiently corrected by our method. Our study indicates that human cleaving embryos provide an efficient base editing window for robust gene disruption and correction.

Keywords: Base editing; Homozygotic nucleotide substitution; Human cleaving embryos.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Embryo Research*
  • Embryo, Mammalian*
  • Gene Editing / methods*
  • Humans