Editing a single nucleotide
Genetic engineers from China have eliminated the congenital disease beta-thalassemia in a human embryo
Anatoly Alizar, Geektimes
While some Western countries prohibit genetic editing of human embryos for religious and other reasons, China has become one of the world leaders in this scientific direction. The direction is very promising, because after deciphering the human genome, an unprecedented amount of information about the markers of point mutations became available to scientists, when the problem is to replace a single base in the DNA chain (the illustration below shows a mutated base A > G, which causes beta-thalassemia).
If gene editing were allowed, people could easily get rid of many of these dangerous and sometimes deadly diseases. This has now been proved by a group of Chinese geneticists.
Gene editing is the best, and sometimes the only way to cure a congenital disease, write the authors of a scientific paper published on September 23, 2017 in the journal Protein & Cell (Liang et al., Correction of β–thalassemia mutant by base editor in human embryos). It not only heals a particular person, but also prevents the transmission of the wrong genes to the next generations.
The authors of the scientific work are from the main Laboratory of Genetic Engineering of the Ministry of Education, the main laboratory of Biocontrol, the main laboratory of Healthy Aging Research of Guangzhou Province, the main laboratory of Reproductive Medicine of Guangzhou and the School of Natural Sciences (all – China), as well as the Department of Biochemistry and Molecular Biology of Baylor Medical College (Houston, USA).
Like other research groups, in this case, for gene editing, scientists initially tried to apply the well-known CRISPR/Cas9 method in combination with homology directed repair (HDR) in three-core zygotes and diploid zygotes, but this method is still difficult to use in real conditions due to low efficiency and undesirable unexpected homological recombinations. Therefore, the researchers used an improved technique that showed high efficiency. They used a base editor based on the CRISPR/Cas9 system and cytidine deaminase (rAPOBEC1).
It is curious that the programmable editing of DNA chains using such an editor was invented in the USA and described in the literature (2016). The editor allows you to very accurately and reliably replace single bases C with T in a DNA macromolecule, and bases G with A. But American researchers were unable to test their invention on humans, so the banner was picked up by Chinese colleagues.
As part of this experiment, geneticists were able to rid the human embryo of congenital beta-thalassemia – this is a fairly common hereditary disease in the Mediterranean countries, the Middle East, India, Central and Southeast Asia. Greater beta-thalassemia occurs in the presence of mutations in both alleles of the beta-globin gene. In the absence or with a sharp decrease in the production of beta chains, hemoglobin A is displaced by hemoglobin F. In the absence of treatment, patients with large beta-thalassemia usually do not live up to five years. The only options for them are allogeneic bone marrow transplantation or permanent blood transfusions throughout their lives, but even in this case they often suffer from concomitant diseases.
Scientists are well aware that the beta-globin gene is located on chromosome 11 at position p15.5, and the disease can be cured by simply correcting the base pairs in this gene at the embryo level, which Chinese researchers have done. Since it is difficult to find an embryo with such a disease in real conditions, scientists have made 20 clones from the patient's skin cells. As a result of the experiment, the successful replacement of base G with base A in one or two alleles was carried out in 8 out of 20 clones. Such efficiency is still insufficient for clinical use, but it exceeds the effectiveness of other methods of gene editing.
Elimination of mutation A>G by replacing the base G
on base A in the DNA editor
This method of editing represents a significant advance compared to conventional genetic editing, because the replacement of individual DNA bases is an ultra–precise method of point editing. Thanks to this, for the first time in the world, a group of Chinese geneticists managed to eliminate a recessive mutation caused by two faulty copies of one gene, that is, mutations in both alleles. This is a significant achievement that opens up completely new prospects for medicine.
The journal Nature writes that scientists from different countries have already published in the scientific press eight papers on the genetic editing of human embryos, five of them in the last two months. No one allowed the embryo to grow for more than 14 days for ethical reasons.
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