Cambridge team uses base editing to study gene function in human embryos for first time

Researchers at the University of Cambridge have used base editing for the first time to study gene function in human embryos, demonstrating that the NANOG gene is essential for the formation of pluripotent cells during the earliest days of development. The study, published in Nature on June 25, marks a milestone in embryo research and has reignited ethical debates over heritable genome editing.eurekalert+1

A Master Gene for Building the Body

The team, led by Professor Kathy Niakan at the Cambridge Loke Centre for Trophoblast Research, blocked NANOG expression in very early-stage human embryos and found that cells could not develop into the epiblast — the layer that gives rise to all cell types in the body, including germ cells and embryonic stem cells. Cells destined to become the placenta and yolk sac, however, were unaffected.eurekalert

"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," Niakan said.eurekalert

The study also revealed that NANOG does not function identically in humans and mice. In mice, loss of NANOG disrupts both the epiblast and the yolk sac, while in human embryos it primarily affects only the epiblast. "Our assumptions about the role of this gene don't transfer neatly across species," said Dr. Katarina Harasimov, a co-author on the study.eurekalert

A More Precise Tool

Base editing changes a single nucleotide base pair without cutting both strands of DNA, reducing the risk of unintended chromosomal damage associated with conventional CRISPR/Cas9. Dr. Oliver Bower, the study's first author, said the precision "allows us to study early human development with greater confidence."biorxiv+1

The work was conducted under a licence from the UK's Human Fertilisation and Embryology Authority using donated IVF embryos cultured for no more than six and a half days.eurekalert

Implications and Ethical Debate

The findings hold promise for understanding early pregnancy loss and improving IVF success rates. Base editing could theoretically be used to correct inherited conditions such as cystic fibrosis in embryos, though this remains illegal in the UK. A separate Columbia University preprint published earlier this month demonstrated base editing to correct disease-linked genes in human embryos, further fueling discussion over whether such techniques could someday lead to heritable genetic changes — or so-called designer babies. Leading gene-therapy organizations have called for a moratorium on clinical heritable editing, with experts stressing that the science remains far from ready for that step.cen.acs+2