Russian geneticist Denis Rebrikov claims that the Chinese have not made a fundamental breakthrough in editing the human embryo. They were ahead, because no one before them had dared to give birth to GMO-children. From a scientific point of view, the Chinese have not made any fundamental breakthroughs. In vitro fertilization (IVF) has been used in medicine for many years, and using the genome editing technology CRISPR method in 2017 alone, more than 3 thousand scientific publications were published. According to the scientist, technically, the Russian group could have transplanted embryos even earlier, and then a genetically modified child would have been born earlier, just Russian doctors go to this slowly, repeatedly checking the safety of the technology.

Recently, researcher He Jiankui from Shenzhen, China, announced that he was able to create the world's first genetically modified people. Changes were made to the twins' DNA that should enable children to resist possible HIV infection. The geneticist changed the embryos to seven couples during the treatment of infertility with one pregnancy at the exit. According to him, the goal was not to cure or prevent a hereditary disease, but to try to give children the ability that only a few naturally possess. Using the CRISPR-Cas9 gene editing tool, he has turned off the CCR5 gene, which forms a protein pathway that allows HIV to enter the cell.

Vice Rector of Pirogov Russian National Research Medical University Denis Rebrikov and his colleagues published a similar study, in which HIV-resistant embryos were created. Now this team is preparing to transplant the edited mother embryo.

The rapid development of CRISPR technologies in recent years has greatly expanded the scope of their application and has contributed to the advancement into clinical practice. Editing the CD4 + T cell genome by knocking out or modifying the chemokine receptor 5 gene (CCR5) has yielded encouraging results in the treatment of HIV-1 infection.

However, besides changing the CCR5 gene in T-cells (to block the development of AIDS in HIV-infected patients), the creation of the CCR5delta32 allele can be used as an element of in vitro fertilization technology (IVF) to protect the fetus of HIV-infected women with a weak response to antiretroviral therapy.

Introduction of the CRISPR-Cas9 system at the zygote stage allows modifying the genome in almost all cells of the body, and this has already been demonstrated for several hereditary diseases. It is important to note that the modified genome will be transmitted to subsequent generations. A modification identical to the natural CCR5delta32 allele will potentially protect the fetus from HIV infection during fetal development, as well as during labor. An additional positive effect could be a person’s lifelong resistance to HIV infection. Russian genetics optimized the CRISPR-Cas9 system in order to create a homozygous 32-nucleotide deletion (similar to the natural CCR5delta32 allele) in the S-phase of a human zygote. Zygotes with an abnormal number of pronuclei unsuitable for in vitro fertilization programs (IVF) were used to edit the genome.

The study was approved by the ethical committee of the NMITS AGP them. V.I. Kulakov (protocol No. 2017/45). All stages of the study (methods) were carried out in full compliance with existing international principles and rules for working with embryos. Written informed consent was obtained from each married couple prior to the transfer of abnormal zygotes to the study. The study included couples in which the absence of CCR5delta32 was shown for both partners.

CRISPR-Cas9-mediated editing of the human zygote genome is an effective method for modifying intracellular DNA, reaching almost 100% elimination of the original sequence in more than half of the embryos taken in the study. The results correlate well with other cases of the use of genome editing systems demonstrating comparable high efficiency.

Over the past two years, there has been an extremely rapid development and update of GE systems. However, the main issue today is the degree of non-target activity of genome editing systems. Only after an unequivocal confirmation of safety, such methods can be applied in real clinical practice.

Based on RNRMU (Pirogov Russian National Research Medical University)

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