Gene editing used to alter DNA of human embryos

Gene editing used to alter DNA of human embryos

After the egg is fertilised, it divides until at about seven days it forms a ball of around 200 cells called the "blastocyst".

Pioneering British scientists have revealed the key role played by a fertility "master gene" after editing DNA in human embryos.

Kathy Niakan and his team said the United Kingdom has a competitive edge in human embryology because the country has a supportive regulatory framework, as well as public and charitable agencies prepared to fund research in the field.

The researchers, based at the Francis Crick Institute in north London, used a technique called CRISPR-CAS9 to remove a gene in very early embryos. The researchers planned to focus first on OCT4, known as a marker for pluripotent stem cells-cells that can become all tissues in the body.

This was the first use of genome editing to study gene function in human embryos, which could help scientists to better understand early development, said the Francis Crick Institute, whose researchers took part in the study. Not only did the blastocyst not form in the majority of embryos that had CRISPR editing, but there were also differences in the placenta-related cells, as well.

The researchers found, without OCT4, the blastocyst couldn't form. They performed this technique on 41 human embryos, then "stopped embryo development" at the seventh day after conception to analyze the results of their actions.

"One way to find out what a gene does in the developing embryo is to see what happens when it isn't working", Dr Kathy Niakan from the Francis Crick Institute said. The findings show that the gene controls the fate of several cell lineages and has a slightly different role in humans than in mice.

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.

Lanner, whose lab is conducting studies with CRISPR of other genes that are crucial for embryo development, points to the importance of painstakingly optimizing the experimental conditions in mouse embryos before moving the studies to human embryos, as Niakan's team had done. "We could maybe use a test of the protein that the embryos secrete into the media, and not manipulate the embryos at all, to increase IVF clinical rates", says Niakan.

Most fertilised eggs fail to develop during IVF for reasons that are poorly understood.

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.

Through this experiment, the team demonstrated the relation between an embryo's development and the OCT4.

Dr Niakan's team was the first to use the editing technique to investigate gene function in human embryos, rather than try to correct defective 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", she added, explaining that their study was only the first step.

Scientists believe that lower than normal OCT4 activity could be why embryos fail to implant successfully, leading to miscarriage. "This paper therefore elegantly highlights the need for further research using human embryos".

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