NEW YORK, NY (Sept. 9, 2026)--A study by researchers at Columbia University Vagelos College of Physicians and Surgeons has found that new cutting-edge techniques can accurately edit genes in human embryos—giving scientists indispensable tools for understanding normal human development—but has also uncovered important risks that currently preclude the use of the techniques in the clinic.
Editing the genome is an essential technique for scientists seeking to understand the genome. Editing genes in human embryos allows us to understand the earliest steps of human development. Early human embryos accrue a surprising amount of DNA damage as they grow, and most human embryos made with IVF stop their development in the first few days.
“By introducing such damage using editors, we are starting to understand how human embryos handle damage in their genomes. Long term, we hope to learn how to prevent genetic and developmental abnormalities during IVF to create more efficient, safer, and more affordable fertility treatments,” says Dieter Egli, the study’s leader and associate professor of developmental cell biology in the Department of Pediatrics.
In the study, published Sept. 9 in Nature , Egli’s team used base editing—a more meticulous genetic editor than earlier techniques—to make changes in individual letters in the DNA of single-cell human embryos. They then followed each embryo’s development for 6-7 days (a stage when IVF embryos can be implanted) to determine if the edit was made correctly and passed on to all cells in the embryo. Remarkably, in some experiments, the editing was 100% successful and development was apparently normal.
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.”
About 10 years ago, Egli’s lab first tried using CRISPR—then a relatively new technique—to edit a gene in early human embryos. CRISPR works like a pair of scissors to cut both strands of a cells’ DNA in order to insert a new sequence. After the cut, CRISPR relies on the cell to glue the broken ends together.
Egli was skeptical CRISPR would work, because his lab had found that human embryos usually bungle the repair of double-stranded DNA breaks.
Unsurprisingly, when his team tried CRISPR to edit human embryos, it mostly failed , deleting large sections of chromosomes and even entire chromosomes as development progressed.
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.
In the new study, Egli’s Columbia team worked with an international team of collaborators and tried base editing to fix single letter DNA mutations in three genes. One gene, called PCSK9 , is linked to high cholesterol and cardiovascular disease. Two other genes, HBG1 and HBG2 , are involved in haemoglobin production, and when mutated can cause blood disorders like sickle cell anaemia and beta-thalassemia.
When performed on fertilized eggs before the first cell division, base editing successfully modified the genome and the changes persisted in 100% of the resulting embryo’s daughter cells.
However, the researchers found that base editing also generated an array of other alterations in unpredictable patterns. Large chromosomal deletions occurred, though at a much lower frequency than seen with CRISPR. “This tells us something about how the type of DNA damage caused by base editors is repaired or fails to be repaired by the cell,” Egli says.
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.
Furthermore, when the mRNA of some base editors was present at high levels in the embryos, the embryos failed to develop, identifying another important risk that would need to be fully understood and avoided for editing to be possible.
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.
In the lab, the new techniques will help scientists understand the biological mechanisms that drive the earliest days of human development.
The Egli lab will use base editing to learn more about the impact of DNA damage during embryogenesis, which may lead to methods to reduce the risk of genetic abnormalities and embryo attrition for patients undergoing IVF. Another research team has already published its use of base editing to discover a protein called Nanog that plays a crucial role in human embryonic development.
“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.
The paper, titled “Highly efficient base editing at PCSK9 and normal human embryo development,” was published in Nature .
All authors: Stepan Jerabek (Columbia and Czech Academy of Sciences, Chanju Jung (Seoul National University), Michelle Kappy (Columbia), Zhao Qiaojin (Columbia), Julie Sung (Columbia), Jimin Kim (Columbia), Marcos Iuri Roos Kulmann (Czech Academy of Sciences and Charles University), Madeleine Bliss King (Arizona State University and University of California Irvine), Mitchell John McAndrew (University of California Irvine), Meng Li (Columbia), Euihyun Kim (Columbia), Sakshi Bhatele (Columbia), Melisa Isado (Columbia), Hong-Su Jang (Seoul National University), Michal Dolezal (Czech Academy of Sciences), Robert Prosser (Columbia), Ning Wang (Columbia), Shuangyi Xu (Columbia), Gue-Ho Hwang (Seoul National University), Iva Pichova (Czech Academy of Sciences), Jia Xu (Genomic Prediction Inc), Diego Marin (Genomic Prediction Inc and Rutgers University), Jae-Sung Woo (Institute for Basic Science, South Korea), Sangsu Bae (Seoul National University), Nathan Treff (Nucleus Genomics Inc), Audrone Lapinaite (University of California Irvine and Rutgers University), and Dieter Egli (Columbia).
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Columbia University Irving Medical Center (CUIMC) is a clinical, research, and educational campus located in New York City. Founded in 1928, CUIMC was one of the first academic medical centers established in the United States of America. CUIMC is home to four professional colleges and schools that provide global leadership in scientific research, health and medical education, and patient care including the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing. For more information, please visit cuimc.columbia.edu .
Nature
Experimental study
Human embryos
Highly efficient base editing at PCSK9 and normal human embryo development
9-Sep-2026
Nathan Treff, Jia Xu, and Diego Marin are shareholders and/or employees of Genomic Prediction, Inc., a company providing chromosomal and SNP analysis for clinical purposes. Stepan Jerabek, Audrone Lapinaite, and Dieter Egli are co-founders of Proofread Therapeutics.