First use of precision editing to study human embryo development reveals role of master gene

Research led by the University of Cambridge Loke Centre 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 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 specialised 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 helps scientists better understand how human embryos develop in the first few days after an egg is fertilised.

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 future help to improve IVF success rates and better understand early pregnancy loss.

Base editing could also potentially be used in future to edit specific genes for debilitating inherited conditions - like cystic fibrosis and Huntington's disease - in human embryos to prevent the conditions being passed on to future generations. However, this would not be legally permissible in the UK 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 Centre 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 modelling. 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 Centre 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 to 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 Centre 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 family, and wanted their surplus embryos, eggs or sperm to be used for research.

The embryos were only cultured in the lab for up to six and a half days after fertilisation, and then allowed to perish.

The study was done under a research licence and strict regulatory oversight from the Human Fertilisation and Embryology Authority (HFEA), the UK Government's independent regulator overseeing fertility treatment and research. The research was also reviewed and approved by Newcastle and North Tyneside Research Ethics Committee.

The study is published today in the journal Nature .

It was conducted by scientists at the University of Cambridge Loke Centre for Trophoblast Research in collaboration with colleagues at Monash University, Newcastle University, Broad Institute of Harvard and MIT, Francis Crick Institute, MRC Laboratory of Molecular Biology as well as clinical collaborators at Bourn Hall Clinic, Newcastle Fertility Centre (part of Newcastle Hospitals NHS Foundation Trust), Assisted Reproduction and Gynaecology Centre, Create Fertility, and Centre for Reproductive and Genetic Health .

This research was primarily funded by Wellcome with additional support from the UK Medical Research Council and Cancer Research UK.

Reference: Bower, O.J. et al: ' Base editing reveals an essential role for NANOG in human embryogenesis. ' Nature, June 2026. DOI: 10.1038/s41586-026-10792-1

What are the epiblast, yolk sac and placenta in the embryo?

The epiblast is a pluripotent cell layer in the early human embryo, which gives rise to all the tissues of the human body.

The yolk sac provides an embryo with nutrients, circulates gases between mother and fetus, and makes cells that turn into important structures such as the umbilical cord. During the first trimester, the period when many pregnancy complications first emerge, the yolk sac performs the role later assumed by the placenta. In IVF treatment, a healthy yolk sac during this window is the strongest predictor of a successful pregnancy outcome.

The placenta is a temporary organ that develops in the uterus during pregnancy and connects the developing embryo to the mother's uterus, acting as a life-support system.

What are pluripotent cells?

Pluripotent cells of the embryo can be used to establish stem cells that have the ability to differentiate into any type of specialised body cell and are widely used in medical research, from disease modelling, cell replacement therapy and drug discovery. This study shows that NANOG is critical to the human embryo's ability to generate pluripotent cells.

What is CRISPR/Cas9?

CRISPR/Cas9 is a genome editing technique that has been used to correct genes in children and adults with conditions including Sickle Cell Disease, certain cancers, and a form of genetic blindness. It's like using a pair of molecular scissors to cut DNA in very precise places and make edits to it.

Scientists had also hoped that CRISPR/Cas9 might be used in future to correct genetic mutations in embryonic cells. At this early stage of development, the genetic changes would then be heritable - meaning that disease-causing genes would be permanently removed and not passed on to future generations of a family.

Previous research by Niakan's team found that using the conventional CRISPR technique to edit genes in embryonic cells leads to chromosomal abnormalities. The team concluded that the older version of the technique should not be used in human embryos for gene correction.