First use of precision editing to study human embryo development reveals role of master gene
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Research led by the University of Cambridge Loke Center for Trophoblast Research has shown that a genome-editing technique can be used to alter a single gene in human embryonic cells, enabling the study of very early human development in unparalleled detail. The study is published in the journal Nature.
The technique, called base editing, is a more precise version of the genome-editing technique CRISPR/Cas9. It can change a single nucleotide base pair—the basic building block of DNA—within a human genome of approximately 3 billion base pairs.
Using base editing, the researchers blocked a gene called NANOG in very early-stage human embryos and found that the cells of the early embryo could not develop into more specialized pluripotent cells called the epiblast, which later form the body.
The results reveal the crucial role of NANOG in the development of human embryos and help scientists better understand how human embryos develop in the first few days after an egg is fertilized.
Without NANOG, the cells that later become the placenta and yolk sac—the tissues that support the developing embryo—could still form.
While human embryo base editing has been previously reported, this is the first time that this technique has been used to study gene function in human embryos. The results show that the extreme precision of the technique reduces the likelihood of unintended chromosomal abnormalities, which can occur with another, more widely used version of CRISPR/Cas9.
Understanding more about the role of genes required for human development, such as NANOG, could in the future help improve IVF success rates and better understand early pregnancy loss.
Base editing could also potentially be used in the future to edit specific genes for debilitating inherited conditions—like cystic fibrosis and Huntington's disease—in human embryos to prevent the conditions from being passed on to future generations. However, this would not be legally permissible in the U.K. at present. Before any future clinical use, extensive safety testing, further development of the technique, and broad public debate and support would be required.
"Base editing represents a significant advance on conventional CRISPR/Cas9 because it carries a far lower risk of causing unintended chromosome errors. Base editing can precisely change a single nucleotide base pair to another in an entire human genome of around 3 billion base pairs—that's an incredible feat," said Professor Kathy Niakan at the University of Cambridge Loke Center for Trophoblast Research, who led the study.
She added, "Our results indicate that the NANOG gene is critical for the development of pluripotent cells, the building blocks that are fundamentally important to human development."
Pluripotent cells can develop into any other type of cell in the body and are widely used in biomedical research, from drug testing to disease modeling. Human embryonic stem cells, which are pluripotent, arise in a part of the developing embryo that has high levels of NANOG activation. This has caused scientists to suspect that NANOG plays an important role in their creation.
"The precision of base editing is a major step from the previous generation of genome-editing techniques. This allows us to study early human development with greater confidence," said Dr. Oliver Bower, a researcher at the University of Cambridge's Loke Center for Trophoblast Research and first author of the study.
He added, "By pinpointing how genes like NANOG control the development of pluripotent cells, we can make stem-cell systems for biomedical research more predictable and reliable."
Human development does not always follow the mouse blueprint
Decades of animal research, particularly in mice, were essential for identifying NANOG as a gene likely to play a major role in early development. But this study shows that NANOG does not function identically in human and mouse embryos.
In previous mouse studies, loss of NANOG disrupted both the epiblast and the yolk sac, a tissue that supports the developing embryo. In this human embryo study, loss of NANOG primarily affected the epiblast, the future body-forming line of cells.
Until now, it has not been possible to directly investigate the function of NANOG in human embryos because the genome-editing techniques available, like conventional CRISPR/Cas9, cause too much unintended damage to the DNA. This work underscores the importance of directly investigating human development.
"We had predicted that the gene called NANOG would have a really important role in human development, given its importance in the development of mouse embryos. What we found was that NANOG functions somewhat differently in humans and mice, which means our assumptions about the role of this gene don't transfer neatly across species," said Dr. Katarina Harasimov, a researcher at the University of Cambridge's Loke Center for Trophoblast Research who was also involved in the study.
Ethical and legal compliance
The embryos, eggs and sperm used in the study were unused samples donated by couples who had undergone IVF treatment. Most donors had completed their families and wanted their surplus embryos, eggs or sperm to be used for research.
The embryos were cultured in the lab for only up to six and a half days after fertilization and then allowed to perish.
The study was done under a research license and strict regulatory oversight from the Human Fertilization and Embryology Authority (HFEA), the U.K. government's independent regulator overseeing fertility treatment and research. The research was also reviewed and approved by the Newcastle and North Tyneside Research Ethics Committee.
Publication details
Base editing reveals an essential role for NANOG in human embryogenesis, Nature (2026). DOI: 10.1038/s41586-026-10792-1. www.nature.com/articles/s41586-026-10792-1
Journal information: Nature
Key medical concepts
Editing, BasePluripotent Stem CellsCystic Fibrosis
Clinical categories
Clinical geneticsObstetrics & gynecology Provided by University of Cambridge Who's behind this story?
Sadie Harley
BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →
Robert Egan
Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →
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