Cambridge Team Uses Precision Base Editing to Reveal NANOG's Essential Role in Human Embryo Development
Base editing knockout of NANOG in human embryos shows it is essential for the epiblast, the tissue that forms the body, arriving alongside a separate disease-gene editing study that has renewed debate over heritable genome editing.
Overview
A team at the University of Cambridge has used base editing, a next-generation form of CRISPR gene editing, to knock out a single gene in early-stage human embryos and show for the first time that it is essential for building the future body. The findings, published in Nature on 25 June 2026, mark the first use of precision base editing to directly study gene function in human embryos, according to a University of Cambridge research announcement. The study lands amid a broader wave of base-editing experiments on human embryos this year, including a separate Columbia University-led project editing disease-relevant genes, that together have reignited debate over how far embryo editing research should go.
What We Know
Researchers led by Professor Kathy Niakan used base editing to block a gene called NANOG in very early-stage human embryos. They found that without NANOG, embryonic cells could not develop into the epiblast — the specialized pluripotent cells that go on to form the entire human body — while the tissues that become the placenta and yolk sac could still form, according to Cambridge.
“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, according to Cambridge and independently corroborated by Medical Xpress, which reproduced the same quote. “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,” she added.
Study co-author Oliver Bower said the precision of the technique was central to the result: “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,” he said, adding that “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,” according to Cambridge.
The result also overturned an assumption carried over from mouse research. Co-author Katarina Harasimov said the team “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,” but “NANOG functions somewhat differently in humans to mice, which means our assumptions about the role of this gene don’t transfer neatly across species,” according to Cambridge. In earlier mouse studies, loss of NANOG disrupted both the epiblast and the yolk sac; in the human embryos, loss of NANOG primarily affected only the epiblast.
The embryos, eggs and sperm used in the study were unused samples donated by couples who had undergone IVF treatment and largely completed their families, according to Cambridge. The embryos were cultured in the lab for up to six and a half days after fertilization before being allowed to perish, under a research license from the UK’s Human Fertilisation and Embryology Authority and approval from the Newcastle and North Tyneside Research Ethics Committee, Cambridge reported. Cambridge said that, until now, it had not been possible to directly investigate NANOG’s function in human embryos because conventional CRISPR/Cas9 causes too much unintended DNA damage.
The Cambridge result arrives weeks after a separate team led by Columbia University’s Dieter Egli used base editing on human embryos for a different purpose: modeling disease-relevant genetic variants rather than studying a developmental gene. Egli’s group edited genomic sites in human zygotes corresponding to PCSK9, which regulates cholesterol, and HBG1/HBG2, which govern fetal hemoglobin, according to Scientific American. The genes were chosen because they are well-studied, not for therapeutic purposes, Scientific American reported. Most edited embryos showed mosaicism, meaning the edit was not present uniformly in every cell, and embryos only survived when the base editor was delivered as a protein rather than as RNA, which caused development to stop, according to Scientific American. Egli’s own base-editing approach, separately described in STAT News, produced “much less incidental genomic damage than what has previously been seen with more standard CRISPR gene editing.”
The Egli work has drawn a sharper mix of scientific and ethical reactions than the Cambridge study. Alexis Komor, deputy director of the Sanford Stem Cell Innovation Center at UC San Diego, said “the cat’s out of the bag,” warning the technique could become “a gateway to embryo editing to do enhancements,” according to Scientific American. Krishanu Saha, a biomedical engineer at the University of Wisconsin–Madison, was more skeptical of the framing: “I would not call it a breakthrough…I find it hard to think about a scenario where this is medicine,” he said, adding that “the real safety involves the birth and long-term follow-up of the child,” according to Scientific American. Egli defended the research’s purpose: “The first goal is knowledge…That often leads to new ways to help people,” he said, according to the same report.
Egli has also drawn a boundary around his own role in the ethical debate that follows his research. “There you stop and let others take over,” he said, in comments carried by STAT News. Paul Knoepfler, a professor of cell biology and human anatomy at UC Davis School of Medicine who writes for STAT, pushed back in the same piece: “I disagree. We scientists need to be deeply involved in the discussions,” he wrote, calling for “at least a temporary moratorium on heritable human gene editing” that would run in renewable ten-year periods while ethical guidelines are established.
What We Don’t Know
Neither study establishes that base-edited human embryos are safe to implant or bring to term; both the Cambridge and Columbia-led embryos were cultured only in the lab and were not transferred for pregnancy. Scientific American reported that most of Egli’s edited embryos showed mosaicism, and researchers have not resolved how consistently the editing outcome could be controlled across cells in a given embryo. The precise magnitude of the disease-relevant edits’ efficiency in the Egli study, and the exact base-editor variant used in the Cambridge NANOG work, were not independently verifiable from the sources available for this article and are not reported here.
Analysis
Taken together, the two projects illustrate two distinct uses base editing is being put to in human embryo research within the same few months: one basic-science application, using a gene knockout to map what a single gene actually does in early human development, and one disease-modeling application, using the same underlying chemistry to introduce or reverse specific genetic variants. Both approaches rely on the same core advantage over conventional CRISPR/Cas9 — avoiding the double-strand DNA breaks that carry a higher risk of unintended chromosomal errors, as both Niakan and Egli’s collaborators separately emphasized. That shared technical foundation is precisely what has widened the ethical debate: a tool precise enough to reliably study or correct a single gene in a human embryo is, in Komor’s framing, also precise enough that its next uses will not necessarily be left to basic researchers to decide alone.