CRISPR used to peer into human embryos’ first days

Heidi Ledford in Nature:

Gene-edited human embryos have offered a glimpse into the earliest stages of development, while hinting at the role of a pivotal protein that guides embryo growth. The first-of-its-kind study stands in contrast to previous research that attempted to fix disease-causing mutations in human embryos, in the hope of eventually preventing genetic disorders. Whereas those studies raised concerns over potential ‘designer babies’, the latest paper describes basic research that aims to understand human embryo development and causes of miscarriage. Published online today in Nature¹, the study relied on CRISPR–Cas9, a gene-editing system that can make precise changes to DNA in the genome. In this case, researchers harnessed CRISPR–Cas9 to disrupt the production of a protein called OCT4 that is important for embryo development.

Researchers have traditionally done such studies in mouse embryos, which are more plentiful and carry fewer ethical considerations than human embryos. But the latest study highlights key differences between the role of OCT4 in human and in mouse embryos, underscoring the limitations of relying on animal models, says stem-cell scientist Dieter Egli of Columbia University in New York City. “If we are to truly understand human embryonic development and improve human health, we need to work directly on human embryos,” he says. “We cannot rely only on inference from model organisms.”

…It soon became clear that normal development had derailed in embryos that lacked normal levels of OCT4. About half of the controls (which had unaltered, normal OCT4 levels) developed to form multicellular embryos called blastocysts. Of the edited embryos with disrupted OCT4 levels, only 19% made it that far. The results will reassure scientists that CRISPR–Cas9 is efficient enough for studies in human embryos, says Fredrik Lanner, a developmental biologist at the Karolinska Institute in Stockholm. “If you do this in mice, you can test hundreds of embryos,” he says. “But you have a limited access to human embryos.”

More here.