Base editor repaired embryo lesions without indels, but mRNA delivery caused frequent arrest
Delivering ABE8e-V106W as a protein at fertilization edited all PCSK9 alleles in human embryos and allowed development to the blastocyst stage, with no insertions or deletions detected. Researchers at Nucleus Genomics, Inc. also derived homozygous edited stem cell lines. Unlike Cas9-induced double-strand breaks, which are genotoxic and cause frequent aneuploidy and large deletions, base editor lesions at PCSK9 and HBG were repaired efficiently. That said, rare on-target chromosome breakage and chromosomal abnormalities did occur. Bystander and off-target editing was mosaic. Introducing the editor as mRNA caused frequent embryo arrest through guide-independent deaminase activity, a problem the authors say currently rules out clinical use in reproduction.
The findings clarify where base editing stands relative to Cas9 in human embryos: more efficient repair, fewer indels, but real developmental risks remain. Mosaicism and embryo arrest from mRNA delivery are not minor footnotes. Researchers working in reproductive genetics now have concrete evidence that protein delivery is the safer route and that the path to any clinical reproductive application requires solving guide-independent deaminase activity first.
Written by the Genomes desk from the primary source cited and linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].