Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-019-1703-6) contains supplementary material, which is available to authorized users.