First use of precision editing to study human embryo development reveals role of master gene | University of Cambridge
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First use of precision editing to study human embryo development reveals role of master gene
Scientists have, for the first time, used an extremely precise genome editing technique called base editing to study gene function in human embryos. They found that a gene called NANOG is essential for forming the future body from an embryo.
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.
Kathy Niakan
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.<br>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.<br>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.<br>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.<br>Without NANOG, the cells that later become the placenta and yolk sac - the tissues that support the developing embryo - could still form.<br>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.<br>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.<br>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.<br>“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.<br>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.”<br>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.<br>“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...