This is us doing genetics
Who in St. Petersburg studies gene mutations and develops medicines against hereditary diseases
Eva Regen, Pavel Merzlikin, online newspaper "Paper"
What diseases can be treated with the help of gene therapy and how drugs are being developed against severe hereditary diseases, why should a geneticist be examined and what mutations should couples planning a child be tested for?
In a partner article with Gazprom Neft, Paper spoke with St. Petersburg residents specializing in genetics – a doctor at the International Center for Reproductive Medicine and an employee of the BIOCAD gene Therapy laboratory.
Alexander Prokofiev, Head of the bioprocess Group of the BIOCAD Gene Therapy Laboratory. Photo: Egor Tsvetkov.
– How are gene therapy drugs being developed?
– Our department is engaged in the development of a completely new generation of medicines, the so-called advanced therapy drugs. My group – the bioprocess group– consists of nine people, including me. She develops technologies for the production of recombinant viral particles, which are necessary for the creation of drugs for in vivo and ex vivo gene therapy (in vivo therapy involves the delivery of a therapeutic gene directly into the cells of the patient's tissue, while in ex vivo cell repair occurs outside the body - approx. "Papers").
In the case of in vivo gene therapy, a viral particle is used as a system for delivering a functional copy of a gene into the patient's body to restore the function of a non-functioning gene. This approach can be used to treat severe hereditary diseases for which there is no adequate therapy, for example, hemophilia, which is currently considered incurable.
World studies show that such treatment is highly effective and has a long-lasting therapeutic effect. We are also developing technologies for the production of recombinant viral particles for ex vivo gene therapy of oncological diseases. In this case, viral particles are used to modify the patient's T-cells in vitro (outside the body – approx. "Paper") and give them the necessary properties for a highly effective fight against cancer cells – this is the so-called CAR-T therapy.
While our products have not yet entered the market. The drugs that we developed first are now at the stage of preclinical trials. We expect that within a few years they will reach the stage of clinical trials. It is difficult to guess when exactly they will enter the market, since no one in Russia has yet launched products for gene therapy using such technologies. There is not even a regulatory framework for this yet.
– How did you get this job?
In high school, I became interested in the exact and natural sciences – primarily biology and chemistry. I have such a mindset: I liked this area for its concreteness and accuracy, clear cause-and-effect relationships. Accordingly, after school I entered the Faculty of Biology of St. Petersburg State University, and towards the end of the second year I started working at the Department of General Physiology, where I studied the molecular mechanisms of muscle regulation.
After my master's degree at St. Petersburg State University, I was offered to continue my studies at the graduate school of the University of Hamburg, where my work slightly changed the vector – from physiology to molecular neurobiology. I participated in a project to study the structure and functions of ion channels. These are proteins that are responsible for conducting nerve impulses in the brain. They are of great interest in the search for new drugs, since a violation in the operation of ion channels can lead to various pathologies – both muscular, neurological, and diseases of the cardiovascular system.
After graduate school, I worked at the technology center at the University of Twente in the Netherlands. There we were developing nanotechnological microchips to study the same ion channels. These devices were planned to be used to create screening systems that can be used in pharmacology.
At the end of this project, I received an offer from Biocade. I decided to return to Russia. I originally had a plan: I wanted to get an education abroad and international experience, but I wasn't going to leave for good. It's just my personal beliefs – I wanted to work in my hometown and benefit at home.
– Why can't anyone do this job?
– You need to have a lot of skills. It is necessary to have broad knowledge in the field of molecular and cellular biology, biochemistry, immunology and genetics. Know a variety of methods, such as cloning, working with DNA and RNA, chromatographic purification methods, be able to work with cell cultures, and so on. We use a wide range of complex methods and the more a person knows and knows how, the better.
At the same time, in addition to knowledge of specific methods and technologies, you need to be in the scientific trend, because everything is changing very quickly in the modern scientific world. It is no longer enough to be a cool, but narrow specialist in a particular field. It is necessary to have interdisciplinary experience, since most of the research is now taking place at the junction of different directions and areas.
It is still difficult to say that our education fully meets such employers' requests. Of course, if a person just went to university and attended all the courses, this is not enough. It is very important in which laboratory and in which department he worked. If you are lucky with this, then the level of graduates in general allows you to start a career in our field, although they will need to be further trained.
In general, I think it is useful for a future scientist to go abroad and see how they work there. Internships, master's or postgraduate studies are priceless. So a person automatically expands his scientific horizons, and he can learn new methods of work, which, perhaps, are not very developed in Russia yet. With such experience, you can return to Russia as a much more mature specialist.
– What will your profession change in the next 50 years?
– The duration and quality of life of patients suffering from severe forms of hereditary diseases will increase due to the entry into the market of new gene therapy drugs, including those based on the principle of genomic editing. There will be new types of personalized medicine for the treatment of oncological diseases.
I think that during the same time, issues regarding the ethics of working with genes will be resolved. Once people were afraid of antibiotics or electricity, now people are afraid of GMOs or work with stem cells. It will take 10-15 years and they will stop. We just need to popularize these areas. It seems to me that all this resistance is due to simple ignorance. People tend to be afraid of what they don't know.
Anna Kinunen, a geneticist at the International Center for Reproductive Medicine. Photo: Valery Zaitsev.
– What does a clinical geneticist do?
– All employees of our center work to achieve one goal – the birth of a healthy child. Since the ICRM is a center for assisted reproductive technologies (ART), the main part of my patients are married couples suffering from infertility.
Therefore, the first stage of my work often consists in analyzing the possible genetic causes of infertility in a particular family. At the initial consultation, I collect an anamnesis, analyze the pedigree, examine patients, determine the scope of the necessary follow-up examination.
The next stage is to assess the risk of having a child with a hereditary pathology. My task is to inform the family about possible and necessary preventive measures. One of the earliest types of prevention of hereditary diseases is preimplantation genetic testing (diagnosis of genetic diseases in the embryo before implantation into the uterus – approx. "Papers"), which is held in our center. After pregnancy, it is advisable for a couple to remain under the supervision of a geneticist at least until the birth of a child.
Today in Russia, married couples planning their first pregnancy without the use of ART rarely turn to a geneticist. The standard minimum examination is karyotyping (analysis of the chromosome set), which both spouses should perform only once in their lives, since the karyotype does not change in humans. In my opinion, this analysis should be recommended to all couples, because on average every 300-400 th person in the world is a healthy carrier of balanced chromosome rearrangement (mutations that change the structure of chromosomes - approx. "Papers"), and he, as a rule, does not know about it. But since a person transfers only half of the chromosomes with the germ cell, there is a high risk of transferring the rearrangement partially, that is, in an unbalanced version. Which can lead to infertility, miscarriages, as well as to abnormal fetal development or even the birth of a child with a chromosomal pathology.
It is also desirable for all couples to be examined for carrying mutations in genes. To date, more than 6 thousand monogenic diseases have been described, which are caused by a "breakdown" (mutation) in specific genes. Depending on the ethnicity of the spouses, you can make a list of the most common hereditary diseases that a couple should check first. Each of us is a healthy carrier of several pathological mutations in different genes, which is not dangerous for the person himself. But if both spouses are carriers of a mutation in the same gene, then the risk of having a child with this disease will be high (25%). The minimum that I recommend checking is mutations in five genes that cause such common hereditary diseases as cystic fibrosis, phenylketonuria, spinal muscular atrophy, nonsyndromic hearing loss and adrenogenital syndrome.
According to the conducted research, in Russia every 50th person is a carrier of a mutation in at least one of these five genes. In our center, we conduct a mandatory examination of sperm and oocyte donors for the most frequent genetic mutations. When they are identified, the donor is excluded from the program.
When detecting fetal pathology, my task is to inform the family about possible options for further actions. The couple has the right to terminate the pregnancy up to 22 weeks or decide to prolong the pregnancy and give birth to an unhealthy child. This is a very difficult decision.
– What is the most difficult part of your job?
– The most difficult thing is communicating with patients and creating a comfortable environment for the family. Most patients come already with some kind of trouble, in a difficult psychological state, so every geneticist should be partly a psychologist. Couples often discuss with me such issues that spouses are not always ready to discuss even with each other alone. I am often consulted by spouses who have survived the death of children, planning the next pregnancy with a healthy fetus.
The psychologist of our center provides great help to us, doctors, and patients. I have the opportunity to refer patients to him when I see that a couple is not coping with their emotions, and we cannot continue to work effectively.
I have been working in the field of genetics since 2009 and still pass everything through myself. There are difficult consultations when I leave the office and realize that I need to recover myself.
– Why can't anyone do this profession?
– In principle, any person who has received the appropriate education can be engaged in genetics. For a clinical geneticist, the main thing in his work is interaction with patients. For a laboratory geneticist – carrying out genetic analyses in the laboratory. It all depends on the inclination of the person.
A doctor of any profession should strive for development and study all his life. Especially in genetics – this area of knowledge is now very actively developing. If you stop following new research and developments, then in a year or two you may simply not understand half of the terms.
– Is it worth doing this business in St. Petersburg?
– Of course it's worth it. We have a strong school of medical genetics and a large number of highly qualified teachers with extensive experience and, most importantly, the desire to share this experience. There are extensive opportunities for laboratory diagnostics of hereditary diseases in our city: we have been cooperating with several laboratories for many years and are personally familiar with their specialists.
Another plus: we have a very beautiful and interesting city that attracts specialists not only from Russian cities, but also from other countries. The city annually hosts a large number of international medical conferences, most of which have sections on genetics.
– What distinguishes this profession from others?
Kinunen:
- The main part of our work, unlike doctors of other specialties, is not treatment. To date, most hereditary diseases are incurable. Our main task is their prevention.
- A person of any age can come to the geneticist for an appointment. If a pediatrician treats children, a therapist works with adults, then we work with a fetus, a newborn, a teenager, an adult, an elderly person.
- A geneticist has a special view of a person, a view in general. Hereditary diseases are characterized by simultaneous damage to several organ systems, as well as the formation of external features – the so–called "stigmas of dysembriogenesis" (fetal development disorders - approx. "Papers"). Therefore, a geneticist needs to conduct an examination and examination of the patient's entire body, collecting changes in different body systems into one whole.
Prokofiev:
- Developments can save people who are now doomed to death. The drugs that we are developing to combat oncological diseases will be used in particularly severe cases – with resistance to standard therapy and relapses. That is, we can help save people who are now doomed.
- You need to be ready to use complex methods and technologies. The projects that we are engaged in are high-tech and innovative and super complex in terms of implementation and the methods that we apply.
Portal "Eternal youth" http://vechnayamolodost.ru