Columbia study finds gene editing in embryos effective but too risky for clinical use

A team of researchers led by Columbia University has demonstrated that base editing can modify genes in human embryos with remarkable precision, achieving 100% accuracy in some experiments, but the study published Wednesday in Nature also exposed a range of safety risks that rule out clinical use for now.cuimc.columbia+1

Precise Edits, Unpredictable Side Effects

The Columbia team, led by Dieter Egli, used base editing — a gentler alternative to traditional CRISPR that swaps individual DNA letters rather than cutting both strands — to target mutations in three genes in single-cell human embryos. One gene, PCSK9, is linked to high cholesterol and cardiovascular disease; two others, HBG1 and HBG2, are involved in haemoglobin production and associated with sickle cell anaemia and beta-thalassemia.news-medical+1

When performed on fertilized eggs before the first cell division, the edits persisted in all of the resulting embryo's daughter cells. But the technique also produced chromosomal deletions, off-target changes, and mosaic patterns of genetic alterations across embryonic cells. At high concentrations of the editor delivered as mRNA, embryos failed to develop entirely.cuimc.columbia+1

"Mosaicism creates a range of possibilities, making it impossible to predict outcomes, and is thus preventing meaningful application for use in the clinic," Egli said.cuimc.columbia

A Clearer Picture of DNA Repair in Embryos

The study is the first to provide a detailed comparison of how human embryos respond to two types of DNA damage. Collaborators at the Czech Academy of Sciences contributed purified protein-based editors, and co-first author Štěpán Jeřábek noted that embryos repaired single-strand DNA damage far more reliably than double-strand breaks caused by conventional CRISPR-Cas9. The researchers also derived stem cells from edited six-day-old embryos, enabling deeper analysis of editing effects across subsequent cell generations.eurekalert

The findings arrive months after a separate team at the University of Cambridge used base editing to study the role of the protein NANOG in human embryo development, published in Nature in June. Together, the studies underscore that base editing is becoming a powerful research tool for early human biology, even as clinical applications remain distant.nature

Drawing Boundaries for a Powerful Technology

"By their very nature, in order to edit a gene, you first have to damage DNA," said Jeřábek. "This intrinsic potential to cause damage is also what confers the risk". Egli added that when safer alternatives exist to prevent genetic disease, "gene editing is not the method of choice".cuimc.columbia

The researchers said they hope the work will help improve IVF outcomes by clarifying how embryos handle genomic damage — and that it will discourage premature clinical use. "I think our study will discourage inappropriate use of these techniques in the clinic, because we clearly demonstrate the risks," Egli said.cuimc.columbia