CRISPR Used in Human Embryos to Probe Gene Function

The research heralds improvements in IVF success Credit Science

Half of the zygotes in the control group developed normally to form blastocysts or multicellular 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.

"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.

For the first time researchers have used genome editing techniques to study gene function in human embryos, revealing the role of a key gene in the embryos' first few days of development, according to a study released on Wednesday by the Francis Crick Institute.

"By understanding the key genes that are involved in the development of the blastocyst, this can really inform our understanding of this important, critical window of human development", Niakan tells NPR.

Niakan and colleagues predicted from earlier work with mice and human embryonic stem cells that the protein OCT4 would be necessary for the epiblast cells to develop correctly.

The study, published in the journal Nature, found fewer than a fifth of the test embryos reached the blastocyst stage without Oct4. Researchers must apply for a license to conduct research, and embryos used for research can not develop for longer than 14 days after fertilization and can not be implanted into a woman's womb.

Dr Niakan said: "One way to find out what a gene does in the developing embryo is to see what happens when it isn't working".

In a first time ever, the UK Human Fertilisation and Embryology Authority granted the researchers permission to use human embryos in their study involving gene editing.

OCT4 may not just be useful in embryo development.

Many experts believe the form of research is pivotal to gaining a better understanding of how humans develop.

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".

Before beginning experiments on human embryos, the scientists spent a year optimizing their work on mice embryos and human embryonic stem cells. "Now we have demonstrated an efficient way of doing this", said Kathy Niakan, one of the Francis Crick Institute authors.

It is hoped the study - using surplus embryos donated by women at an IVF clinic - will help the one in seven couples who have difficulty having a baby.

Those advances are still many years away, says Niakan. Lower than normal OCT4 activity may explain why embryos sometimes fail and lead to miscarriages. This summer, researchers at Oregon Health and Science University fertilized eggs using sperm carrying a genetic defect, then deployed CRISPR to correct it, as The Scientist reported, following on 2015 work using CRISPR in embryos by a research team in China. "This paper therefore elegantly highlights the need for further research using human embryos".

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