The explosive growth of human genomic data has revealed unprecedented numbers of disease-causing point mutations. Repairing such mutations may offer the best, and in some cases, only cure for genetic diseases. We and other groups have sought to correct disease mutant by combining CRISPR/Cas9 and homology directed repair (HDR) in human tripronulcear zygotes and diploid zygotes. However, low efficiency, mosaicism, off-target cleavage, and unintended homologous recombination (between target site and endogenous homologous genomic DNA sequence) remain obstacles that hamper the clinical applications of such approaches (Kang et al., 2016; Liang et al., 2015; Tang et al., 2017). In a recent report, it was found that diploid human zygotes, distinct from pluripotent cells, tends to repair DNA double strand break (DSB) using endogenous homologous sequence (Ma et al., 2017), consistent with what we have found in human tripronuclear zygotes (Liang et al., 2015). In the study, highly efficient repair of the mutant allele was achieved using the wild-type (WT) allele in heterozygous human zygotes through CRISPR/Cas9 (Ma et al., 2017). However, homozygous mutant embryos could not be repaired in way because of the lack of WT alleles. Additionally, recombination may occur with similar but not identical endogenous sequences, leading to unexpected mutations, as we found in human tripronuclear zygotes in which HBB recombined with HBD (Liang et al., 2015). Using base editors to directly repair point mutations may represent an efficient and highly specific alternative.