One of the leading Russian experts in the fieldmethods of molecular biology and genetic engineering Denis Vladimirovich Rebrikov in an interview with the journal Nature told about plans to conduct an experiment on the creation of children with edited genes. He stated that he was ready to repeat the experience of the Chinese geneticist He Jiankui, during which the Lula and Nana twins were born. According to Rebrikov, he is considering the possibility of implanting genetically-edited embryos before the end of the year, if he receives the appropriate approval of three departments, including the Ministry of Health of the Russian Federation.
What is CRISPR-Cas9?
CRISPR-Cas9 is a technologygenome editing based on the principles of the immune system of bacteria (they are able to find and eliminate viral DNA). CRISPR-Cas9 includes a guide RNA molecule that finds the desired chromosome piece, and the Cas9 enzyme that cuts DNA. If at this moment to add a normal copy of the gene, it is embedded in the right place. The process resembles text editing when part of a sentence is deleted and other words are inserted in its place.
Editing of genes in Russia
The purpose of the experiment of the Russian biologist will bea modification of the same gene that the Chinese genetic engineering specialist, CCR5, worked on. In an interview with Nature, Rebrikov said that he was going to turn off the gene in the embryo that encodes a protein that allows HIV to enter the cells of the body. Embryos will subsequently be implanted in HIV-positive mothers who do not respond to standard therapy. It is noted that the risk of transmission to the child in this case will be higher, but if during the procedure it turns out to successfully disable the CCR5 gene, this risk will be significantly reduced.
Recall that He Jiangkui, in turn, tookcells of HIV-positive fathers, and then transplanted the resulting embryos to HIV-negative mothers. There was no practical sense in this, which in turn, among other things, was another reason for the criticism of Chinese genetics by the world community of scientists. He's work caused a flurry of criticism among the scientific community and led to the appearance of an open letter in which scientists called for a moratorium on conducting experiments on the genetic editing of embryonic cells. Rebrikov argues that his method of modifying a gene will prove more beneficial, less risky and more ethically justified and acceptable to society.
Rebrikov adds that he has already reached an agreement with a local HIV center, where he is going to attract women volunteers who are ready to participate in his experiment.
Nature magazine asked for comments onabout the planned experiment of the Russian scientist to other researchers who, as expected, expressed concern about Rebrikov's plans. For example, Jennifer Dudna, a molecular biologist at the University of California at Berkeley and one of the pioneers of the CRISPR-Cas9 gene-editing method, says that this technology is not yet fully understood and is not ready for use in clinical situations.
"I am not surprised at such statements, but this news is very disappointing and at the same time disturbing," the scientist added.
Even if the experience is successful, a small riskcontamination will remain. And we still do not know exactly how this will affect the life of a person as a whole. For example, in a recent study, carriers of both copies of mutant CCR5 found the risk of earlier death compared with carriers of the normal gene.
"Before scientists start takingAttempts to implant genetically modified embryos are necessary to conduct a transparent, opening debate about the scientific and ethical acceptability of such experiments, ”says geneticist George Daly of Harvard Medical School.
Russian specialists also expressed their disagreement with similar experiments.
“This is potentially very dangerous. The possibility of the appearance of even one sick person already imposes a ban on all this, ”said geneticist Igor Dolotovsky, commenting on the VIEW of the VIEW, commenting on the plans of biologist Denis Rebrikov to create genetically modified children.
Molecular geneticist Konstantin Severinov, withcontacted by the authors Nature noted that in Russia it would be very difficult to obtain approval for such experiments. After all, it is necessary to take into account not only the opinion of state structures, but also the church, which opposes the editing of genes. And this greatly reduces the chances of getting approval - at least in the coming years.
And yet the most important question is how realistic is the perspective Rebrikov draws?
Dolotovsky believes that the experiment is technically possible, but the problem lies in the ethical part of the issue.
“Everything is possible, the Chinese did, our scientist can too. Here is an ethical question - experiments on people, changes in the human genome. And technically, a lot can be done, ”added Dolotovsky.
According to Rebrikov himself, to whom the editors of Hi-News.ru turned for comment, the ethical side of the question is an extremely important aspect.
“The ethical side is an extremely important question for usit will certainly be necessary to obtain all approvals from the Ethics Committees and from the controlling structures. But the fact is that there are clinical situations where the ethics of such a (gene-editing) approach cannot be doubted. These are cases where 100% of children in a couple of parents will suffer from a severe genetic disorder. Such situations are infrequent, but exist. When both parents are homozygous for violating the same gene, leading to a hereditary disease (for example, deafness), ”noted Rebrikov.
Why are people afraid of genetic experiments?
One of the reasons why the topicGenetically modified embryos have caused such heated debate in the global community because if we allow such experiments now, the resulting “GMO children” will grow and be able to pass on their modified genes to future generations. Scientists generally agree that the technology of gene editing will one day be able to help in the complete elimination of genetic diseases such as sickle cell anemia and cystic fibrosis, but today a lot more additional research is needed.
In addition, there are safety concerns.gene editing of embryos in a more general sense. Rebrikov states that his experiment, in which he, like the Chinese geneticist He, is going to use the CRISPR-Cas9 genome editing method, will be completely safe. However, scientists believe that the use of CRISPR-Cas9 in its current form can cause "untargeted" mutations in other genes, without capturing the necessary, which are the goal of the editing process. Thus, it is possible that genes, for example, that are responsible for suppressing the growth of tumors, may be turned off.
According to Rebrikov, he is developing a methodwho can guarantee such blunders. The scientist plans to publish the preliminary results of this work during the month, possibly in the bioRxiv online scientific reprint repository or in a peer-reviewed journal.
When asked to comment on this statement to our portal, the author of the project responded as follows:
We learned to check security correctly.the CRISPR system used, precisely defining its off-target (unfocused, - ed.) activity on embryos with previously known genome. This, as far as I know, is not available to anyone in the world. And this allows us to go to practical application consciously, and not in the way that He did. ”
In turn, scientists, for which commentsNature's authors appealed, skeptical about Rebrikov's claims about solving the problem of non-target mutations and the possibility of realizing only target ones, in which only the necessary genes will be edited and exactly as planned.
Last year in the journal Bulletin of the Russian State Medical University, where heis the editor-in-chief, Rebrikov published an article in which he argued about developing a method capable of disabling both copies of the CCR5 gene (by removing part of 32 base pairs) in more than 50 percent of cases.
However, Jennifer Dudna, a molecular biologist at the University of California at Berkeley, expressed skepticism about these results.
“The data that I saw show that it’s not easy to control the process of DNA recovery,” says the scientist.
The geneticist of the Australian National University, Gaetan Burgio, agrees with her, noting that in the editing process there are possible deletions and insertions that are difficult to determine.
Incorrect editing can lead tothat the gene will not be shut off improperly, which in turn will leave the cell still unarmed against HIV, or cause a gene mutation that will function in a completely different and unpredictable way, Burdge said.
Moreover, Burdge, the unmutated geneCCR5 has may have many useful functions that have not yet been fully studied. For example, scientists have previously determined that the gene seems to provide some protection against complications caused by infection with West Nile fever, as well as influenza.
“We know a lot about the role of the CCR5 gene in the entry of HIV into cells, but we don’t know much about its other functions,” adds Burggio.
CRISPR perspectives in Russia
Denis Vladimirovich Rebrikov (Nature photo)
We also asked Denis Vladimirovich about what are the prospects for the CRISPR-Cas9 technology and whether it is capable of defeating all genetic diseases.
"Hereditary diseases will not winCRISPR-Cas9, and pre-implantation genetic diagnosis (PGD). The fact is that, as indicated above, editing is justified only in the event of a breakdown of all four alleles (for a given pair of parents). This is an extremely rare situation. One in a million. But children with hereditary diseases are born very often (almost 1% of newborns!) And it is very easy to win: for a couple of parents who have a risk of having a sick child (because we know their genetics in advance (from somewhere)) conduct IVF and PGD in order to select a healthy embryo. And no CRISPR-Cas9 is needed! For some reason, few non-specialists understand this. ”
To the question of how things are generally going on with CRISPR-Cas9 research in Russia, and what role the government plays in them, Rebrikov answered that, in general, so far so good.
“On the general background - things are fine. Many groups work with this technology in all areas: plants, animals, microorganisms. There are developers of new nucleases like Cas9 and modifiers of the existing ones. There are exploratory studies of new similar systems. Everything is normal here. ”
“The state has now announced a large program for the development of genetic technologies. So far, the money has not gone through it, but it will definitely be a plus for development and CRISPR-Cas9 as well. ”
About how he would describe the technology CRISPR-Cas9 and what is his attitude to her Rebrikov replied:
“This is another molecular genetic technology. Over the past 50 years, many of these have been created, and this one is no steeper than PCR or sequencing (for which the Nobel Prizes were given, by the way). Just another technology to work with DNA and genes. I believe that in the quite foreseeable future (years 10), humanity will come to a directed change in the human genome in order to improve it (and perhaps to alternate cloning and editing the genome - this is most effective). ”
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