A team led by Dieter Egli at Columbia University reports that base editors can make precise single-letter changes in human embryos at two disease-relevant targets — PCSK9 and HBG — without the chromosomal abnormalities and large deletions seen in earlier CRISPR-Cas9 attempts. The work was posted to bioRxiv on June 1, 2026, and has not been peer reviewed. All findings are preclinical: edited embryos were used for laboratory analysis, not implantation.
The central contrast is mechanistic. According to the abstract, double-strand breaks made by CRISPR-Cas9 in early human embryos “result in frequent aneuploidy and large deletions, revealing a repair deficiency in early human embryos and limiting the clinical application of this technology.” Base editors instead introduce DNA nicks and mismatches. The authors report that editing at PCSK9 and HBG was efficient and, unlike Cas9-induced breaks, “did not result in either chromosomal abnormalities or large deletions.” Small insertions or deletions were rare, and off-target activity depended on the guide RNA. This is an absence-of-detected-harm result in a small, non-peer-reviewed study, not a demonstration that the approach is harm-free.
A note on the targets: the abstract collapses the paralogous fetal-hemoglobin genes HBG1 and HBG2 into a single label, HBG. Secondary coverage in Nature describes three genes edited — PCSK9, HBG1, and HBG2 — so the preprint’s “two targets” and the “three genes” reported elsewhere refer to the same work.
Delivery decided viability
Method mattered. According to the abstract, delivering the editor as protein at fertilization or at the pronuclear stage “allowed normal development to the blastocyst stage and the derivation of edited stem cell lines,” whereas delivering it as RNA “resulted in early embryo arrest.” Edits were mosaic — some cells carried the change, others did not — and Egli told Nature the base editors “can have damaging effects on the embryo,” signaling the approach is not clinically ready.
“These base editors — they can have damaging effects on the embryo. So why would you use it if you don’t fully understand that?” — Dieter Egli, to Nature
Geneticist Fyodor Urnov was sharply critical, telling Nature that the work reads like a how-to manual for “baby improvers” pursuing forays beyond the ethical pale, and noting that IVF combined with genetic screening can already prevent transmission of many heritable conditions. Bioethicist Hank Greely warned that affluent individuals could set up a private IVF and genetic-testing lab “for probably a handful of millions of dollars” to pursue embryo editing. Others judged the work more careful than prior efforts: Greg Neely told Nature it was “less reckless, more careful and ethical than previous attempts.” This is a research report, not clinical guidance.