Recent research has unveiled crucial master genes, specifically Nanog, that govern human fetal development. This discovery was achieved through targeted modifications of fertilized egg DNA utilizing advanced CRISPR base editing technology.

This breakthrough has the potential to significantly elevate success rates in in vitro fertilization (IVF) treatments. As noted by Kathy Niakan from Cambridge University, understanding the early stages of human development is essential not just for enhancing IVF but also for propelling stem cell biology forward. “Greater insights will have far-reaching benefits for regenerative medicine and stem cell research,” she adds.

While the involvement of Nanog in embryonic development has been established through animal studies, it is essential to note that its role differs significantly in humans compared to other species like mice. Once fertilization occurs, cells differentiate into three primary types: those that will become the placenta, the yolk sac, or the embryo itself. Disabling the Nanog gene in mouse fertilized eggs using base editing resulted in zero cells developing into yolk sac progenitors. Base editing is a nuanced version of CRISPR that modifies one DNA base at a time, reducing the risk of unintended genetic mutations compared to earlier CRISPR methods, clarifies Niakan.

Conversely, inactivity of the Nanog gene in human eggs donated from IVF patients led to no cells maturing into embryo-forming cells, underscoring its critical role in initiating human developmental processes.

Despite appearing normal under microscopic examination, embryos lacking Nanog fail to implant successfully. Niakan states, “Approximately half of the embryos that appear viable based solely on their shape still cannot implant.” Identifying vital markers or genes, such as Nanog, could potentially enhance IVF success rates, she notes.

Niakan’s research represents one of the pioneering studies utilizing base editing on human embryos. The initial endeavors began as early as 2017. However, previous studies focused on embryos discarded due to abnormalities, thereby limiting applicability to healthy embryos. Recently, Dieter Egli presented findings at Columbia University, detailing base editing in two-cell embryos in a preprint study.

Niakan clarifies, “Our goals were fundamentally distinct. We aimed to decipher the functions of critical genes in human embryos, setting a new precedent for this type of research.” In contrast, Egli’s work primarily seeks to correct mutations associated with diseases.

Yet, Egli expressed skepticism regarding Niakan’s findings, asserting that there is no substantial evidence of Nanog‘s functional importance in human embryogenesis. Niakan, however, argues that her team conducted further research to support their conclusions.

All three studies converge on the understanding that CRISPR-based editing techniques pose significantly fewer risks than traditional CRISPR methods previously employed. However, according to Mary Herbert, a collaborator with Niakan’s team, we remain distant from the ethical application of CRISPR base editing for creating genetically edited children due to current technological limitations. “The technology isn’t ready for that yet,” she emphasizes.

A significant challenge remains the phenomenon of mosaicism, where gene edits are inconsistently successful across various cells in an embryo. This implicates that even corrected mutations may not prevent potential diseases in the resulting child. For instance, Egli’s team faced an 80% mosaic rate in their embryos. Niakan’s team, by implementing edits earlier in the fertilization process, encountered a lower but still concerning mosaic rate of 50%.

Niakan morally cautions against attempts for child gene edits at this stage but remains open to future possibilities: “I advocate for more basic research that is accessible for public discussion.”