Highly efficient base editing at PCSK9 and normal human embryo development.

Base editing at PCSK9 in human embryos achieves high efficiency with normal development, supporting the derivation of homozygous edited stem cell lines.

• Why it matters: Understanding safer genome editing methods is crucial because Cas9-induced DNA breaks cause genotoxic effects, including aneuploidy and large deletions, threatening embryo viability and clinical applications.
• What they did: Researchers delivered ABE8e-V106W as a protein at fertilization to target PCSK9 and HBG loci in human embryos, achieving editing at all alleles without insertions or deletions, and supporting development to the blastocyst stage.
• The result: While base editing was efficiently repaired and supported embryo development, off-target mosaicism and chromosomal abnormalities were observed, indicating current limitations for clinical reproductive use.