In a first, human embryos edited to explore gene function

In a first, human embryos edited to explore gene function

In a first, human embryos edited to explore gene function

Following fertilization, an egg starts to divide and after about seven days, it becomes a ball-shaped structure called a blastocyst, which later forms the placenta.

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

The team of scientists from the Francis Crick Institute in London used CRISPR-the experimental biomedical technique that utilizes snippets of bacteria as a pair of "molecular scissors"-to slice out the gene responsible for producing a protein known as OCT4".

"In humans, (OCT4) not only maintains the embryo, but other tissues are affected and the blastocyst does not form", said Ludovic Vallier, a stem cell biologist at the Wellcome Trust Sanger Institute who co-authored the research.

The failures of fertility treatments could be down, in part, to a reliance on mouse studies, which until now have been seen as the best way to work out the role of genes during embryonic development - and why things sometimes go wrong.

The study team used CRISPR/Cas9 to "turn off" the production of one particular gene, known as the OCT4.

The study, published in the journal Nature, found fewer than a fifth of the test embryos reached the blastocyst stage without Oct4.

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

The researchers had to apply to the Human Fertilisation and Embryology Authority, an institution set up in the United Kingdom that rigorously reviews proposed embryo-editing research, Vogel reports for Science.

Niakan's team is the first in Britain to have edited the DNA of human embryos, with just a handful of such experiments having been performed in China and the US. As well as human embryo development, OCT4 is thought to be important in stem cell biology. "Now we have demonstrated an efficient way of doing this", said Kathy Niakan, one of the Francis Crick Institute authors. 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. But, this is the first research to target human growth and development.

Lead author Kathy Niakan (Francis Crick Institute, London) says she hopes the technique can be used by others to identify a whole host of genetic factors that affect pregnancy, but are now poorly understood: "One way to find out what a gene does in the developing embryo is to see what happens when it isn't working".

"It may take many years to achieve such an understanding, our study is just the first step", Niakan said.

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.

Vallier believes this further highlights human development is very specific and different from that of other species, meaning techniques based on animal models will have limitations. The experiments helped the researchers learn about fundamental human biology in a way they could not through research on mice.

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