June 25, 2026

expert reaction to base editing revealing role of master gene (NANOG) in embryo development

A study published in Nature looks at base editing and the role of a key gene in embryo development. 

Dr Helen O’Neill, Associate Professor, Reproductive and Molecular Genetics, Institute for Women’s Health, University College London (UCL), said:

“Though headlines may rush to form a narrative that this paper is about creating gene-edited babies, it is a paper about using the most precise tools we currently have to ask one of the most fundamental questions in biology: how does a human embryo make the first cells that will become the fetus, the placenta and the yolk sac?

“This study uses adenine base editing to alter NANOG, a gene long known from stem cell and animal studies to be central to pluripotency. The striking finding is that when NANOG is disrupted in human embryos, the epiblast (the cell population that forms the embryo proper), fails to form normally. Yet the human embryos still retain primitive endoderm-like cells, in a way that differs from mouse embryos. That matters because it shows, once again, that human development cannot simply be inferred from mouse development.

“The true value of genome editing in human embryos is threefold. First, as we see from this paper, it allows us to understand the genetic rules that govern the very earliest stages of human life. Secondly, it can help us understand why so many embryos in IVF fail to develop, arrest, implant or progress, despite appearing morphologically acceptable. Thirdly, in the longer term, it may help us think more clearly and compassionately about a very small group of patients with serious inherited conditions for whom preimplantation genetic testing is not enough.

“The paper itself is appropriately cautious. The numbers are small, the embryos are not transferred, and there are still unresolved questions about mosaicism, off-target effects, developmental competence and whether safety can ever be demonstrated to the level required for clinical use. But it does show that base editing may be a less disruptive way to study gene function in embryos than older CRISPR approaches that create double-strand DNA breaks.

“The debate around embryo editing is often framed as if the only possible endpoint is designer babies. That framing misses the actual scientific and clinical value. The first role of genome editing in embryos is not enhancement, it is understanding. Understanding the embryo is the foundation for improving IVF, reducing embryo loss, and eventually supporting families carrying serious genetic disease who may currently go through repeated IVF cycles and still have no unaffected embryo to transfer.

“This paper should be seen as an important basic science advance, not a clinical green light. It strengthens the case for carefully regulated human embryo research, because it shows that studying human embryos directly can reveal biology that animal models do not fully capture. If we want safer IVF, better embryo selection, and more informed options for patients with inherited disease, we need this type of careful, transparent and ethically governed research.”

Prof Robin Lovell-Badge FRS FMedSci, Group Leader, Francis Crick Institute, said:

“We sometimes like there to be a sense of mystery, but little can be done to solve problems without knowledge; moreover, knowing how something works does not detract from wonderment, it adds to it. Given all the things that can go wrong between having a fertilised egg and a healthy baby (and happy parents), such that this path fails in about 70% of cases, the more understanding we have of the early steps of human embryo development, the better chance we have of reducing distress, disappointment and sometimes debilitating disorders.

“The work from Oliver Bower and others associated with Kathy Niakan’s lab is an important example of both how the research should be done as well as uncovering new knowledge about the first week or so of our beginnings. They focussed on a gene called NANOG, known from studies carried out in mice to play an important role in both the early epiblast, a group of cells that will go on to form the embryo proper, and the yolk sac, which is one of the extraembryonic tissues that, along with the placenta, supports the former. The most direct way to study the role of a specific gene is to inactivate it, and methods based on the use of CRISPR/Cas9 provide a direct and efficient way to do this. However, standard CRISPR methods that create double-strand breaks in DNA rely on cellular mechanisms of DNA repair that all too frequently lead to chromosome damage, as shown previously by the Niakan lab and others. This can make it both challenging to draw firm conclusions and wasteful of valuable human embryos. The authors therefore chose to use base editing, a precise method to alter single nucleotides (‘letters’ in the code). [N.B. this is not the first attempt, but it was carried out with a high degree of rigour and with statistically valid results.] Bower et al show that the methods are both precise and efficient in the context of human embryos.

“Furthermore, by introducing the base editing components along with the sperm during IVF (by intracytoplasmic sperm injection), they also largely avoid mosaicism, where the editing occurs after the first cell division such that only a proportion of cells carry the edit, which can also complicate interpretation of results. With respect to NANOG function, they find that it is required for the epiblast, and it is therefore also essential for human embryo development at an early stage, but that it is dispensable for the development of the extraembryonic endoderm that gives rise to the yolk sac. This adds to the evidence that the genes and mechanisms operating during early mouse and human embryo development can be substantially distinct, making it inappropriate to rely too much on results obtained with the former to understand the latter.

“Although focussed on the role of NANOG in the early embryo, the work does relate to the notion of heritable genome editing, specifically by showing that base editing is very efficient, precise (with rigorous choice of guide RNAs), and can be used in a way that reduces concerns about mosaicism. These are all parameters that need to be close to perfect if the methods were to ever be used to create edited babies. They are not there yet, and even if they were, this should not be attempted without appropriately robust review, oversight and knowledge of the extent of public acceptance and qualifications, and it would have to be legal, which it is not in most jurisdictions.

Prof Dusko Ilic, Professor of Stem Cell Sciences, King’s College London (KCL), said:

“This is an elegant and technically ambitious study that addresses a fundamental question in human developmental biology: how the cells that will ultimately form the foetus are established in the early embryo. The findings are important, but they should not be overinterpreted.

“The work also shows the potential of base editing as a research tool, but it does not demonstrate that embryo editing is safe for clinical use. Likewise, any relevance to infertility, implantation failure or pregnancy loss remains prospective. The immediate value of the study is mechanistic, not clinical.”

Dr Norah Fogarty, UKRI Future Leader Fellow and Lecturer, Centre for Gene Therapy & Regenerative Medicine, King’s College London (KCL), said:

“This is a well-designed and thorough investigation into the use of base editing as a research tool in human embryos. Kathy Niakan and her team draw on their long-standing expertise in human embryonic stem cells and mouse embryology to robustly “quality control” the base editing machinery and assess its specificity and ability to knock out NANOG’s function. The team used a combination of the gold standard methods to get the most information out of each embryo used in the project in their assessment of the role of NANOG in embryo development. The edited embryos were compared with previously published datasets of unedited control embryos to increase the sample size, giving further confidence in the results. There have been a few studies already looking at the use of base editing in human embryos. However these studies were limited in that they largely used tripronuclear embryos which are developmentally and chromosomally abnormal. In contrast, this study uses embryos that are surplus to clinical requirements, or generated from donor gametes, but are otherwise developmentally normal.

“In the near-term, this study elegantly demonstrates that base editing is a tool for human embryo research, allowing us to specifically investigate the role of genes involved in development. Human reproduction is highly inefficient: for reasons that remain incompletely understood: out of 100 fertilised eggs, around 50 fail to reach the blastocyst stage, and of those, a further proportion fail to implant. With advances in genomics technologies like single cell RNA- and genome-sequencing (as used in this paper), alongside emerging in vitro models of early development and implantation (within the legal limit of 14 days post-fertilisation) researchers have unprecedented opportunities to investigate the mechanisms governing early human development. Such discovery research has the potential to inform future clinical advances.

“The authors are clear that more research is needed before base editing could be used in a clinical setting. They also emphasise that, even if clinical translation becomes feasible, there are important ethical and regulatory considerations, and that public engagement and support will be essential. In the future, genome editing may offer an option for patients to prevent passing on genetic disorders, especially in cases where it is not possible to produce healthy embryos for preimplantation genetic testing.

“Overall, this paper reinforces the UK’s position as a global leader for technically and ethically rigorous discovery research using genome editing to understand the earliest stages of human embryo development.”

‘Base editing reveals an essential role for NANOG in human embryogenesis’ by Bower, O.J et al. was published in Nature at 16:00 UK time on Thursday 25^th June 2026. 

DOI: https://doi.org/10.1038/s41586-026-10792-1

Declared interests

Dr Helen O’Neill:I have no conflicts (my work at Hertility is entirely unrelated). 

Prof Robin Lovell-Badge:Kathy Niakan and I are were colleagues at the Francis Crick Institute, where Oliver Bower began his PhD studies. I was a member of his PhD thesis committee, and will have provided advice throughout at least the earlier stages of his project.

Prof Dusko Ilic:No conflicts of interest.

Dr Norah Fogarty:Norah Fogarty was a postdoctoral fellow in the lab of Kathy Niakan and is the first author of the paper Fogarty, N., McCarthy, A., Snijders, K. et al. Genome editing reveals a role for OCT4 in human embryogenesis. Nature 550, 67–73 (2017). https://doi.org/10.1038/nature24033.

This Roundup was accompanied by an SMC Briefing.