Scientists have disabled a gene in a human embryo

© Illustration RIA Novosti . Alina Polymineralic embryo (left) and a fetus with a disabled gene Oct4 (right)Scientists have disabled a gene in a human embryo© Illustration by RIA Novosti . Alina Polyanina

American genetics was first used genomic editor CRISPR/Cas9 in order to turn off a critical gene in the human embryo and study its role in the development of the embryo in the first seven days of its existence. The results of their experiments were published in the journal Nature.

«As far as I know, this is the first experiment in which we were able to successfully disable one of the genes responsible for the development of the embryo, and to understand what role it plays in this process. We have uncovered a number of unexpected effects occurring when disconnecting Oct4 in embryos of mice in the future we will try to understand why this is so,» said James Turner (James Turner) from the Institute of Francis Crick, London (UK).

Two years ago in the scientific community began to creep rumors that a number of Chinese scientists and their American colleagues have conducted a series of experiments to edit and replace defective genes in human embryos, the editorial office of news Nature told a number of unnamed molecular biologists.

In April 2015, these rumors were confirmed – Chinese scientists published a paper in the journal Protein & Cell, in which they described the results as a whole rather unsuccessful attempts to adapt rapidly gaining popularity system for genome editing CRISPR/Cas9 for the manipulation of human DNA.

This year American scientists under the leadership of Socrata Mitalipov announced the first successful genome editing of embryos using the CRISPR/Cas9. This genetic operation allowed them to replace the defective gene that causes the hypertrophy of the heart, in its correct version, and in theory, to protect future children from sudden death.

Turner and his colleagues made the next logical step in this line of experiments, adapting CRISPR/Cas9 for the study of the role individual genes play in the development of the human embryo, learning how to turn them off before the fertilized egg begins to divide.

As a first objective scientists chose gene Oct4 is one of the four «magic» of DNA, Nobel laureate open Sinha Yamanakai in 2006, forced the inclusion of which transformerait adult cells. stem cells of the embryo.

As explained by Turner and his colleagues, this gene, as today’s scientists believe, plays a critical role in the development of the embryo in the first seven days of his life, when the egg divides several times and becomes so-called a blastocyst, the initial ball of the embryo from the shell which is formed by the placenta, and the inner part of – the child.

«Most of the fertilized eggs, as shown by the first experiments on artificial insemination, stops its development and dies, at this stage, only 50% of them survive. We have long been interested in which genes control this process, and thanks to CRISPR/Cas9, we now have the opportunity to find the answer to this question,» added Katie Niacin (Kathy Niakan), Turner’s colleague.

Questions of duty and ethics

High probability of death of the fetus, according to scientists, is forcing today’s doctors and patients of reproductive clinics to use not one, but several dozen eggs during their insemination. Very often this leads to the fact that part of the egg remains «extra» that allows scientists to use them in experiments.

Received four dozen such cells, scientists have tried to disable the gene Oct4 in them, using one of the latest versions of CRISPR/Cas9, which Niakan, Turner and their colleagues have adapted to work inside of the embryo.

«We have taken great care to check that edit the genome with CRISPR has not made any unnecessary changes to the structure of the DNA of the embryo, and not «turned off» other genes in addition to Oct4. We literally spent several months searching for similar mistakes and found them, but, of course, in the future, we plan to conduct additional checks of this kind,» explained Niakan, answering the questions of the RIA «Novosti».

As shown by this experiment, Oct4 does play a critical role in the development of the embryo. Disabling it led to the fact that the number of oocytes that reached the blastocyst stage decreased by more than 2.5 times, and most of the surviving fetuses were able to «hang» until this phase for the reason that the genomic editor deleted only one but not both copies of Oct4.

In addition, these experiences, according to her, led to several unexpected results that biologists did not record in conducting similar experiments on the eggs of mice. For example, Niacin, Turner and their colleagues found that Oct4 controls the growth of stem cells of the embryo, but also «pieces» of the future placenta, which never occurs in embryos of rodents.

According to Turner, the same technique can be used to study the work of other genes, and to search for other mistakes in their work, which can lead to death of the embryo or the emergence of problems in embryonic or reprogrammed stem cells. All this will help scientists to find new methods of treatment of diabetes and other diseases, the development of which part of the body’s cells die.

«Why do our donors agreed to donate eggs? They are well aware about the pros they carry, that without such experiments the procedure of artificial insemination would be impossible. By agreeing to these victims, they hope that these experiments will help to solve other problems associated with the birth of children,» concludes Niacin.

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