Highly efficient gene editing of PCSK9 with normal development in human embryos

Editing at all PCSK9 alleles was achieved in human embryos using ABE8e-V106W protein, supporting development to the blastocyst stage.

• Cas9-induced DNA double-strand breaks in human embryos are linked to frequent aneuploidy and large deletions.
• Base editing at the PCSK9 and HBG loci resulted in no detected insertions or deletions.
• Rare on-target chromosome breakage and chromosomal abnormalities occurred during the editing process.
• Editing effects were mosaic, showing variability at bystander and off-target sites.
• Introducing the editor as mRNA led to frequent embryo arrest due to unintended activity.

Simplified