Research led by the Rourke Center for Trophoblast Research at the University of Cambridge has shown that single genes in human embryonic cells can be changed using genome editing techniques, allowing researchers to study the very early stages of human development in unparalleled detail.
This technology, called base editing, is a more precise version of the genome editing technology CRISPR/Cas9. It has the potential to alter single nucleotide base pairs (the basic building blocks of DNA) within the approximately 3 billion base pair human genome.
Researchers used base editing to block a gene called NANOG in very early-stage human embryos and found that cells in the early embryo were unable to develop into the more specialized, pluripotent cells called the epiblast, which later form the body.
The results reveal an important role for NANOG in human embryo development and help scientists better understand how human embryos develop in the first few days after an egg is fertilized.
Without NANOG, cells that would later become the placenta and yolk sac (tissues that support embryonic development) could still form.
Although human embryonic base editing has been reported previously, this is the first time this technique has been used to study gene function in human embryos. The results show that the extremely high precision of the technology reduces the chance of unintended chromosomal aberrations that can occur with another, more widely used version of CRISPR/Cas9.
Further understanding the role of genes essential for human development, such as NANOG, may help improve IVF success rates and improve our understanding of early miscarriage in the future.
Base editing could also be used in the future to edit specific genes for debilitating genetic diseases in human fetuses, such as cystic fibrosis and Huntington’s disease, to prevent the diseases from being passed on to future generations. However, this is not currently legal in the UK. Extensive safety testing, further development of the technology, and extensive public discussion and support will be required before future clinical use.
“Base editing represents a significant advance over traditional CRISPR/Cas9 because it carries a much lower risk of introducing unintended chromosomal errors. Base editing can precisely change a single nucleotide base pair to another throughout the human genome of approximately 3 billion base pairs. This is an incredible feat,” said Professor Cathy Niacan from the Rourke Center for Trophoblast Research at the University of Cambridge, who led the study.
He added: “Our results show that the NANOG gene is important for the development of pluripotent cells, a fundamentally important component of human development.”
Pluripotent cells can grow into other types of cells in the body and are widely used in biomedical research from drug testing to disease modeling. Pluripotent human embryonic stem cells arise in a part of the developing embryo that has high levels of NANOG activation. This led scientists to suspect that NANOG might play an important role in its production.
The accuracy of base editing is a major advance compared to previous generations of genome editing technology. This will allow us to study early human development with more confidence. ”
Dr. Oliver Bower, Research Fellow, Roarke Trophoblast Research Center, University of Cambridge, and lead author of this study
He added: “Identifying exactly how genes like NANOG control the development of pluripotent cells can make stem cell systems for biomedical research more predictable and reliable.”
Human development doesn’t necessarily follow the mouse blueprint
Decades of animal research, particularly in mice, were essential to identifying NANOG as a gene that likely plays a major role in early development. However, this study shows that NANOG does not function in the same way in human and mouse embryos.
In previous mouse studies, loss of NANOG destroyed both the epiblast and the yolk sac, the tissue that supports the developing embryo. In this study of human embryos, loss of NANOG primarily affected the epiblast, the cell lineage that will form the future body.
Until now, it has not been possible to directly investigate the function of NANOG in human embryos because available genome editing techniques, such as traditional CRISPR/Cas9, cause too much unintended damage to DNA. This study highlights the importance of directly investigating human development.
“We predicted that a gene called NANOG would play a very important role in human development, given its importance in mouse embryonic development. What we discovered is that the function of NANOG is somewhat different in humans and mice. “This means that our assumptions about the role of this gene do not translate well across species,” said Dr Katarina Harasimov, a researcher at the University of Cambridge’s Rourke Center for Trophoblast Research, who also participated in the study.
Ethics and legal compliance
The embryos, eggs, and sperm used in the study were unused samples donated by couples undergoing IVF treatment. Most donors had completed their families and wanted to use their extra embryos, eggs and sperm for research.
The embryos were incubated in the lab for up to six and a half days after fertilization, and then killed.
The study was carried out under a research license and strict regulatory oversight from the Human Fertilization and Embryology Authority (HFEA), the UK government’s independent regulator that oversees infertility treatment and research. The study was also reviewed and approved by the Newcastle and North Tyneside Research Ethics Committee.
The study is published today in the journal Nature.
it was The study was carried out by scientists from the Roark Trophoblast Research Center at the University of Cambridge, in collaboration with colleagues at Monash University, the Broad Institute of Harvard University and the Massachusetts Institute of Technology, the Francis Crick Institute, the MRC Laboratory of Molecular Biology, and clinical collaborators at Bourne Hall Clinic, Newcastle Fertility Centre, Center for Assisted Reproduction and Gynecology, Create Fertility and the Center for Reproductive and Genetic Health..
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Reference magazines:
Bower, O.J., R. others. (2026). Base editing reveals an important role for NANOG in human embryogenesis. nature. DOI: 10.1038/s41586-026-10792-1. https://www.nature.com/articles/s41586-026-10792-1
