Efficient PCSK9 base editing in human embryos raises potential but safety concerns linger
Researchers delivered ABE8e-V106W base editor as a protein at fertilization to human embryos, achieving editing at all PCSK9 alleles and supporting development to the blastocyst with homozygous edited stem cells; no insertions/deletions were detected, though rare chromosomal abnormalities occurred. Bystander and off-target edits were mosaic, and delivering the editor as mRNA caused embryo arrest. While base-editor–induced lesions are efficiently repaired compared with Cas9 breaks, current safety concerns prevent clinical use in reproduction.