,Highly efficient base editing in human tripronuclear zygotes

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Dear Editor,There are hundreds of disease-causing single-gene mutations,mainly caused by single-nucleotide substitutions or point mutations rather than small insertions/deletions (indels),and often there are no cures for these diseases.By introducing the CRISPR/Cas9 system into mouse zygotes,disease-causing mutations could be corrected,leading to the production of healthy adult animals (Long et al.,2014;Wang et al.,2013;Wu et al.,2013;Yang et al.,2013).Several studies have demonstrated that CRISPR/Cas9-mediated gene editing could also introduce precise genetic modifications in early human embryos (Kang et al.,2016;Liang et al.,2015;Tang et al.,2017).However,indels rather than singlenucleotide substitutions are obtained frequently,because most DNA double-strand breaks (DSBs) produced by programmable nucleases are repaired by error-prone non-homologous end-joining (NHEJ) rather than homologous recombination (HR) using a template donor DNA.
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