Base editing reveals an essential role for NANOG in human embryo lineage specification.

Decades of research in mouse models have provided valuable insights into the role of transcription factors that regulate early development, however translating these findings to human embryos has been limited by ethical, technical and biological constraints.

Functional studies of key transcription factors in human embryos have been hindered by nuclease-based genome-editing approaches that often induce genotoxicity, such as aneuploidy1-3. To overcome this limitation, we applied adenine base editing (ABE8e)4,5 to efficiently and precisely target an exon splice donor site, resulting in a splicing defect and a functional knockout of the transcription factor NANOG. This work represents the first application of base editing to study a developmental regulator in human embryos.