What the efficiency side measured

Delivering ABE8e-V106W as a protein at fertilization achieved editing at all PCSK9 alleles. Embryos developed to the blastocyst stage, homozygous edited stem cell lines were derived, and no insertions or deletions were detected. In a cardiology clinic the name PCSK9 travels with cholesterol lowering; the measurement here is of a fertilized cell's genome, not of a drug.[1]

The weight of that result comes from a comparison. In human embryos, Cas9-induced DNA double-strand breaks are genotoxic, causing frequent aneuploidy and large deletions. Base editor-induced lesions are efficiently repaired, which moves the failure mode away from chromosome loss and towards the precision of the edit and the way the molecules enter the cell.[1]

The second half of the same experiment

Editing at bystander and off-target sites was mosaic. Rare on-target chromosome breakage and chromosomal abnormalities occurred. Introducing the editor as mRNA caused frequent embryo arrest due to guide-independent deaminase activity. All three findings come from the same experiment as the efficiency figure.[1]

Mosaicism is not an abstract defect for a clinician. It means the sequence read in one cell of an embryo may differ from the sequence in the cell beside it, so a result from a single-cell sample may not represent the whole. Genuinely different editing between cells is not the only explanation: an editor delivered as protein and still active through the first divisions can produce a similar picture. Separating the two requires measuring bystander and off-target sites in individual cells of the embryo.[1]

The one useful sentence for a clinic

The authors' own conclusion is the most useful sentence for a clinic: undesirable consequences for the genome and development can occur, currently precluding clinical use in reproduction. If the next human embryo study delivers the editor as a protein and reports how far bystander and off-target editing varies between cells of the same embryo, then what the efficiency figure covers becomes measurable too.[1]