New base editing techniques accurately modify genes in human embryos

But the editing sometimes caused unpredictable changes and is not safe to use in the clinic. Editing human embryos has the potential to give people who carry disease-causing mutations an opportunity to have healthy children through IVF. "But given our findings, it is currently not possible to do so safely," says Egli.

"As a scientist, the first goal is to uncover new knowledge, which we hope will lead to new ways to help people. But identifying the risks is just as important, because it draws the boundaries for meaningful use of a powerful technology. I think our study will discourage inappropriate use of these techniques in the clinic, because we clearly demonstrate the risks."

Human embryos are difficult to edit accurately

Egli was skeptical CRISPR would work, because his lab had found that human embryos usually bungle the repair of double-stranded DNA breaks.

Base editing is better, but still causes inadvertent damage

In the past few years, scientists have developed next-generation gene editors that are gentler on DNA. These new base editors work more like a pencil with an eraser, removing one letter from a single strand of the DNA and replacing it with another.

The base editor also made changes at some additional sites in the genome as the embryo developed, including in the vicinity of the intended change, resulting in embryos with a mosaic of genetic alterations. When mosaicism occurs naturally, the impact to the embryo varies. "Mosaicism creates a range of possibilities, making it impossible to predict outcomes, and is thus preventing meaningful application for use in the clinic," says Egli.

Editing applications

Egli still sees promise long term in gene editing human embryos to help people who otherwise can't have a healthy child. "It would be far more efficient to edit disease-causing genes in embryos than to apply gene editing later on, when the mutation has amplified in billions of cells, and after the disease has already manifested," he says.

The problems with base editing that prevent clinical use won't be easy to fix. "By their very nature, in order to edit a gene, you first have to damage DNA," says Stepan Jerabek, a research scientist in Egli's lab and lead author on the new paper. This intrinsic potential to cause damage is also what confers the risk. "When other technologies without this risk are available to prevent disease, gene editing is not the method of choice," Egli adds.

"We also don't know very much about how genomic instability in early development affects our health as adults. New mutations can arise on their own, DNA is being repaired because of spontaneous damage, and that's very important to understand. Editing tools applied in human embryos could very well help us understand health and disease in many different areas," Egli says.

Source:

Columbia University Irving Medical Center

Journal reference:

Jerabek, S., et al. (2026). Highly efficient base editing at PCSK9 and normal human embryo development. Nature. DOI: 10.1038/s41586-026-11118-x. https://www.nature.com/articles/s41586-026-11118-x