Reacción a "A new version of CRISPR, base editing, reveals a key factor in human embryo development"

This is a well-designed and thorough investigation into the use of base editing as a research tool in human embryos. Kathy Niakan and her team draw on their long-standing expertise in human embryonic stem cells and mouse embryology to robustly “quality control” the base editing machinery and assess its specificity and ability to knock out NANOG’s function. The team used a combination of the gold standard methods to get the most information out of each embryo used in the project in their assessment of the role of NANOG in embryo development. The edited embryos were compared with previously published datasets of unedited control embryos to increase the sample size, giving further confidence in the results. There have been a few studies already looking at the use of base editing in human embryos. However these studies were limited in that they largely used tripronuclear embryos which are developmentally and chromosomally abnormal. In contrast, this study uses embryos that are surplus to clinical requirements, or generated from donor gametes, but are otherwise developmentally normal.

In the near-term, this study elegantly demonstrates that base editing is a tool for human embryo research, allowing us to specifically investigate the role of genes involved in development. Human reproduction is highly inefficient: for reasons that remain incompletely understood: out of 100 fertilised eggs, around 50 fail to reach the blastocyst stage, and of those, a further proportion fail to implant. With advances in genomics technologies like single cell RNA- and genome-sequencing (as used in this paper), alongside emerging in vitro models of early development and implantation (within the legal limit of 14 days post-fertilisation) researchers have unprecedented opportunities to investigate the mechanisms governing early human development. Such discovery research has the potential to inform future clinical advances.

The authors are clear that more research is needed before base editing could be used in a clinical setting. They also emphasise that, even if clinical translation becomes feasible, there are important ethical and regulatory considerations, and that public engagement and support will be essential. In the future, genome editing may offer an option for patients to prevent passing on genetic disorders, especially in cases where it is not possible to produce healthy embryos for preimplantation genetic testing.

Overall, this paper reinforces the UK’s position as a global leader for technically and ethically rigorous discovery research using genome editing to understand the earliest stages of human embryo development.