BioTechniques News
Tristan Free
For the first time, researchers have used a genome editing technique called base editing to identify a master gene that is essential for human embryo development.
Marking the first application of base editing to study a developmental regulator in human embryos, University of Cambridge (UK) scientists knocked out the pluripotency gene NANOG, demonstrating its integral role in very early human development and enabling the study of this complex process like never before.
Understanding how cells are specified and maintained in the very early stages of human embryonic development has huge implications for regenerative medicine, as well as the study of infertility and pregnancy loss. Mouse models have been vital in pinpointing transcription factors involved in early development; however, similar research in human embryos has been hindered by various ethical, technical and biological complications.
Conventional nuclease-based genome-editing approaches, such as CRISPR, rely on creating double-strand breaks and, as a result, can induce unintentional chromosome errors, rendering them unsuitable for use in humans. Base editing, meanwhile, can make targeted changes to a piece of DNA, modifying a single nucleotide without generating double-strand breaks. Despite offering a lower-risk option for investigating the role of genes required for development, it has never before been used to study gene function in human embryos.
Adenine base editing demonstrates profound impact on rare disease
Precision DNA editing has targeted the root cause of severe childhood epilepsy in a preclinical study.
That is, until the team behind the recent study applied adenine base editing to knock out NANOG. Targeting an exon splice donor site and introducing a splicing defect, the researchers demonstrated that loss of NANOG disrupts pluripotent epiblast specification, which sends cells down a pathway toward becoming either primitive endoderm (yolk sac) or trophectoderm (placenta). The approach, they detail, did not trigger genotoxicity and showed limited off-target editing.
“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,” study lead Kathy Niakan concluded.
Crucially, it appears that the role of NANOG in humans differs slightly from that in mice – loss of the gene in rodents disrupts both the epiblast and endoderm, whereas human embryos retain primitive endoderm-like cells – underscoring the importance of human models in developmental biology.
Although there is still a long way to go, and a number of issues that need to be addressed, before base editing is signed off for clinical use, this study highlights its potential as a research tool, allowing us to study early human development with greater confidence than previous genome editing techniques have allowed.
In future, this may pave the way toward improved fertility treatments, as Helen O’Neill, an Associate Professor in Reproductive and Molecular Genetics at University College London (UK) who was not involved in the research, explained to the Science Media Centre: “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.”
“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.”
The post World-first gene editing application unveils master regulator of human embryo development appeared first on BioTechniques.
Powered by WPeMatico