A team at the University of Cambridge has used a next-generation gene-editing tool to study how a single gene shapes the earliest days of human life — a breakthrough that could improve IVF outcomes and advance biomedical research.
For the first time, scientists have deployed a highly precise form of genome editing to investigate how genes function inside a living human embryo, and the findings are already rewriting what researchers thought they knew about our earliest moments of existence.
A team led by the University of Cambridge’s Loke Centre for Trophoblast Research used a technique called base editing — a more refined successor to the widely known CRISPR/Cas9 method — to disable the gene NANOG in very early-stage human embryos. The results, published June 25 in the journal Nature, confirm that NANOG plays an indispensable role in forming the epiblast, the cluster of cells that eventually gives rise to the entire human body.
What Base Editing Actually Does
Standard CRISPR/Cas9 works by cutting both strands of the DNA double helix, which can introduce unintended chromosomal errors that muddy research results. Base editing sidesteps this by chemically converting a single nucleotide — one letter in a genetic alphabet roughly 3 billion letters long — without cutting the strand at all. That distinction makes an enormous difference when researchers are trying to isolate the effect of one specific gene.
Senior author Kathy Niakan, the Mary Marshall and Arthur Walton Professor of the Physiology of Reproduction and director of the University of Cambridge Loke Centre for Trophoblast Research, described the method’s potential in straightforward terms.
“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,” Niakan said in a news release.
She added that the team’s data make clear how central NANOG is to the process: “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.”
What Happened When NANOG Was Switched Off
When researchers blocked NANOG, the embryos still produced cells destined to become the placenta and the yolk sac — both of which support a developing embryo during pregnancy. But the epiblast, the tissue layer that would normally go on to form the body itself, failed to develop properly. In short, the embryos could build their support structures but not the thing those structures were meant to sustain.
First author Oliver Bower, a researcher at the Loke Centre, emphasized how the method’s reliability changes the kind of conclusions scientists can confidently draw.
“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,” Bower said in the news release.
He also pointed to downstream benefits for the broader research community: “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.”
Humans Are Not Just Bigger Mice
One of the study’s most striking findings is that NANOG does not behave the same way in human embryos as it does in mouse embryos — a reminder that decades of animal research, while invaluable, don’t always translate cleanly to human biology.
In previous mouse studies, disabling NANOG disrupted both the epiblast and the yolk sac. In humans, the disruption was largely confined to the epiblast. That divergence matters because so much of what scientists assumed about NANOG’s function in humans was extrapolated from rodent models.
“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,” added co-corresponding author Katarina Harasimov, a researcher at the Loke Centre.
This species-specific difference underscores why studying human embryos directly — rather than relying solely on animal models — is scientifically necessary, even if it is ethically complex and heavily regulated.
Why This Matters for Students and Young Researchers
Pluripotent cells — the type whose formation NANOG appears to control — are among the most important tools in modern biomedical science. Because they can transform into virtually any cell type in the body, they are used in drug development, disease modeling and regenerative medicine research. Any advance in understanding how pluripotent cells are formed and regulated has ripple effects across multiple fields of study.
More immediately, the findings could have clinical relevance. A clearer picture of which genes govern the earliest stages of human development may eventually help fertility specialists improve IVF success rates and better understand why some early pregnancies fail. The embryos used in this study were surplus samples donated by couples who had completed IVF treatment, cultured in the laboratory for no more than six and a half days before being allowed to perish — a process conducted under a research licence and the strict regulatory oversight of the Human Fertilisation and Embryology Authority.
Looking further ahead, base editing’s precision opens a theoretical door to correcting inherited conditions — such as cystic fibrosis or Huntington’s disease — before birth. The researchers are careful to note, however, that such clinical applications are not currently legal in the United Kingdom, and would require extensive safety trials, further technical refinement, and wide-ranging public debate before any such step could be considered.
A Collaborative Effort
The study was conducted in collaboration with researchers at Monash University, the Broad Institute of Harvard and MIT, the Francis Crick Institute, and the MRC Laboratory of Molecular Biology, along with clinical partners at Bourn Hall Clinic, Newcastle Fertility Centre and several other reproductive health centers across the United Kingdom.
Source: University of Cambridge