Screenshot of a time-lapse video that shows the first five days of embryo development. The embryo on the left is unedited, the right has been edited to prevent the production of the OCT4 protein. Credit: Kathy Niakan/Nature

For the first time in the UK, researchers have used genome editing technology to examine the function of a specific gene in human embryos.

The team, led by researchers at the Francis Crick Institute, also included colleagues from Cambridge University, Oxford University, the Wellcome Trust Sanger Institute, Seoul National University and Bourn Hall Clinic.

The team focused on OCT4, a protein that normally gets activated within the first few days of human embryo development. The protein’s role is not yet fully understood, but it does release an initial “set of instructions” to cells to keep progress embryo development.

Using CRISPR-Cas9, the researchers “turned off” the gene that produces OCT4 and observed what happened to 41 embryo development over the next seven days.

The embryos used for the study were donated from couples who had a surplus after IVF treatment.

A healthy embryo can transform from one cell to about 200 within the first week of development. During this time, the blastocyst also begins to form. Within the blastocyst, the group of cells “decide” to remain as part of the growing embryo or become one of two other structures¾the placenta or yolk sac.

But, as the researchers report in Nature, the blastocyst is incapable of fully forming without OCT4, and essentially implodes. The findings suggest that weakened OCT4 activity may help explain the cause of some miscarriages, and the reasoning behind why many IVF embryos fail to make it past this critical point in development.

“These findings suggest that targeting OCT4 in human embryos reduces both viability and quality of blastocysts,” the team wrote in the study.

The team found that 47 percent (eight out of 17) of the control group embryos survived through the blastocyst stage, compared to 19 percent of the CRISPR-edited ones.

CRISPR-Cas9 only emerged within the last five years, but is already considered a revolutionary technique in biomedical research. Previous experiments using CRISPR to alter the DNA of humans have been conducted in China, Sweden and the U.S., despite the ethical debate that surrounds this type of research.

But this latest study is the first to examine the role of a specific gene in early embryonic development. 

This type of basic research can provide a foundation of knowledge on early human development, and identify the root causes of when something goes wrong. Answering these fundamental questions could lead to improved fertility treatments, according to the team.

"We were surprised to see just how crucial this gene is for human embryo development, but we need to continue our work to confirm its role," said Norah Fogarty, from the Francis Crick Institute, first author of the study. "Other research methods, including studies in mice, suggested a later and more focused role for OCT4, so our results highlight the need for human embryo research."

The team spent more than a year perfecting their techniques with mouse embryos and human embryonic stem cells before switching to work on human embryos.

The study was done under a research license, and strict regulatory oversight from the Human Fertilisation and Embryology Authority (HFEA), the UK Government's independent regulator overseeing infertility treatment and research, according to the Francis Crick Institute