Genome Editing: Pros and cons
Alexandra Bruter, <url>
The scientists who wished to remain anonymous told the staff of the news department of the journal Nature that some scientific journals that also wished to remain anonymous are currently considering the possibility of publishing works on editing the genome of human embryos (Ethics of embryo editing divides scientists).
This topic is generally quite acute and has been discussed frequently lately (Don't edit the human germ line). As usual, as many scientists – so many opinions. And, of course, not only scientists have their own opinion on the issue. The excitement is caused by the fact that an opportunity has appeared. But the understanding of whether to use this opportunity, and, if so, how exactly, how often and for what – did not appear. To date, in countries where scientists have such a technical capability, regulatory authorities are more likely to prohibit such experiments. Out of 22 Western European countries, manipulations with the genome of human embryos are prohibited in 15. There is no direct ban in the United States, but the relevant committee of the National Institutes of Health has stated that it will not currently accept applications for such projects, and it is the main source of large research grants in the field of life science in the United States.
Genome editing itself is not unheard of. But until now, only the genomes of human somatic cells have been edited for practical purposes.
California-based company Sangamo BioSciences introduces a method of HIV therapy/AIDS, based on the modification of the genome of T-lymphocytes. To enter the lymphocyte, the virus needs to have a CCR5 receptor on the surface of the lymphocyte. There are a number of people who have this mutation from birth. Such people are usually resistant to HIV infection. The symptoms of immunodeficiency caused by the virus are due to the fact that the virus penetrates into the T-lymphocytes and multiplies there, and the cells die from this. Backups of the virus can be stored in other cells of the body, but the symptoms of the disease are caused by the death of T-lymphocytes. Most lymphocytes do not live long, their population is constantly being updated due to stem cells living in the bone marrow. The researchers hope that by removing the gene encoding the CCR5 receptor from the lymphocyte progenitor stem cells, they will be able to rid people infected with HIV of the symptoms of the disease. Although these people are likely to be carriers of the virus for a long time (perhaps all their lives), they will be able to do without having unpleasant side effects of antiretroviral therapy, which otherwise they would have to take for life.
Clinical trials of the treatment of beta-thalassemia using genome editing should begin this year. This disease is caused by a mutation in the hemoglobin gene and can be cured if it is corrected in the stem cells of the bone marrow – the precursors of red blood cells.
To date, two fundamentally different methods of genome editing have been developed. One was created earlier, but the other is better.
First, genetically engineered nucleases were invented. In nature, many cellular processes require the interaction of proteins with nucleic acids. In particular, the entire regulation of transcription (i.e. gene activity) is based on the fact that special proteins interact with strictly defined DNA sequences. Usually, domains are responsible for interacting with DNA in proteins, called "zinc fingers" for the shape and the need for zinc atoms to stabilize the structure. Since there are a great many of them in nature, it was not difficult for scientists to learn how to design proteins that recognize any DNA sequence they need. By combining the domain responsible for DNA recognition with the domain that can cut DNA, scientists have obtained an enzyme capable of cutting DNA at a pre-specified location.
A newer genome editing technology used for the first time for this purpose in 2013 is the CRISPR/Cas9 system. This system is also borrowed from nature, or rather from bacteria. For them, it works something like acquired antiphage (antiviral) immunity. Having met with the virus once, the bacterium leaves fragments of the viral in its genome. RNA with the necessary signal sequences can be synthesized from these fragments. If the same virus enters a bacterial cell again, the RNA synthesized by the bacterium interacts with the viral genome according to the principle of complementarity, and a special bacterial enzyme Cas9 is able to cut such interacting structures. If you deliver to the cell a genetic construct encoding RNA, a complementary gene that needs to be corrected, the Cas9 enzyme and a corrected copy of the gene, then they cope on their own. This method is effective, easy to use and, most likely, it was he who struck the spark from which the flame of the revolution in the field of genome editing flared up.
Before you ask yourself whether it is possible to edit the genomes of human embryos, you need to think about whether it is necessary.
In fact, the need for such editing is rare today. When it comes to preventing a couple from having a child with a genetic disease, in vitro fertilization and subsequent embryo selection are most often enough. Only those embryos that do not carry mutations will be implanted into the mother. Perhaps if genome editing was the only way to avoid having a child with the disease, it would be resolved faster.
All other "cons" considerations are divided into security considerations and ethical considerations.
It is difficult to guarantee that the correction of the genome will have time to occur before the division of the fertilized egg (although the CRISPR/Cas9 system is more reliable in this sense than zinc fingers), and if the correction occurs after, then some cells can retain the old genotype, and some can acquire a new one. It will not be possible to find out before the birth of the child, the long-term consequences of this are unknown. The possible mutagenic effect should be studied separately, in animal experiments.
The considerations "against" the ethical plan are also quite strong. Many people think it is unacceptable for parents to pre–order the eye color and character traits of their future children (see the note "Scientists have proposed to declare a moratorium on experiments with interference in human DNA before the adoption of the Code of ethics" - VM).
To date, the following picture is emerging: editing the genome of human embryos is prohibited in most countries, but it is not necessary. Perhaps when we accumulate more knowledge about the role of genetics in some diseases in which it is not obvious today, and at the same time there will be more evidence of the safety of the technique, retrogrades who believe that editing should be banned solely for ethical reasons will remain in the minority.
Portal "Eternal youth" http://vechnayamolodost.ru19.03.2015