Researchers have demonstrated highly efficient base editing at the *PCSK9* and *HBG* loci in human embryos, achieving editing in all *PCSK9* alleles with protein delivery at fertilization. While embryos supported development to the blastocyst stage and derived homozygous edited stem cell lines, the technique is not yet viable for clinical reproductive use due to off-target effects and developmental issues.
Scientists evaluated DNA repair outcomes at nicks and mismatches introduced by base editors in human embryos. Delivering ABE8e-V106W as a protein at fertilization achieved editing at all *PCSK9* alleles. No insertions or deletions were detected, but rare on-target chromosome breakage and chromosomal abnormalities occurred.
However, editing at bystander and off-target sites was mosaic, and introducing the editor as mRNA caused frequent embryo arrest due to guide-independent deaminase activity. The research indicates that, unlike Cas9-induced DNA breaks, base editor-induced lesions are efficiently repaired. Despite this, undesirable consequences for the genome and development currently preclude clinical use in reproduction.
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