CRISPR-Cas9 genome editing shows that the protein OCT4 is essential in very early days of human embryo development.

Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human embryos, which could help scientists to better understand the biology of our early development.

The team used genome editing techniques to stop a key gene from producing a protein called OCT4, which normally becomes active in the first few days of human embryo development. After the egg is fertilised, it divides until at about seven days it forms a ball of around 200 cells called the blastocyst. The study found that human embryos need OCT4 to correctly form a blastocyst.

“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 Dr Norah Fogarty from the Francis Crick Institute, first author of the study.

“One way to find out what a gene does in the developing embryo is to see what happens when it isn’t working. Now we have demonstrated an efficient way of doing this, we hope that other scientists will use it to find out the roles of other genes. If we knew the key genes that embryos need to develop successfully, we could improve IVF treatments and understand some causes of pregnancy failure. It may take many years to achieve such an understanding, our study is just the first step,” said Dr Kathy Niakan from the Francis Crick Institute, who led the research.

The research was published in the journal Nature and led by scientists at the Francis Crick Institute, in collaboration with colleagues at Cambridge University, Oxford University, the Wellcome Trust Sanger Institute, Seoul National University and Bourn Hall Clinic. It was chiefly funded by the UK Medical Research Council, Wellcome and Cancer Research UK.

The team spent over a year optimising their techniques using mouse embryos and human embryonic stem cells before starting work on human embryos. To inactivate OCT4, they used an editing technique called CRISPR/Cas9 to change the DNA of 41 human embryos. After seven days, embryo development was stopped and the embryos were analysed.

The embryos used in the study were donated by couples who had undergone IVF treatment, with frozen embryos remaining in storage; the majority were donated by couples who had completed their family, and wanted their surplus embryos to be used for research. The study was done under a research licence and strict regulatory oversight from the Human Fertilisation and Embryology Authority (HFEA), the UK Government's independent regulator overseeing infertility treatment and research.