Biotechnology – medicine of the future. Biotechnology: about the most important and promising things in science Traditional biotechnology

The discipline that studies how organisms are used to solve technological problems is what biotechnology is. Simply put, it is a science that studies living organisms in search of new ways to meet human needs. For example, genetic engineering or cloning are new disciplines that use both organisms and the latest computer technologies with equal activity.

Biotechnology: in brief

Very often the concept of “biotechnology” is confused with genetic engineering, which arose in the 20th–21st centuries, but biotechnology refers to a broader specificity of work. Biotechnology specializes in modifying plants and animals through hybridization and artificial selection for human needs.

This discipline has given humanity the opportunity to improve the quality of food products, increase life expectancy and productivity of living organisms - that is what biotechnology is.

Until the 70s of the last century, this term was used exclusively in the food industry and agriculture. It wasn't until the 1970s that scientists began using the term "biotechnology" in laboratory research, such as growing living organisms in test tubes or creating recombinant DNA. This discipline is based on sciences such as genetics, biology, biochemistry, embryology, as well as robotics, chemical and information technologies.

Based on new scientific and technological approaches, biotechnology methods have been developed, which consist of two main positions:

  • Large-scale and deep cultivation of biological objects in a periodic continuous mode.
  • Growing cells and tissues under special conditions.

New biotechnology methods make it possible to manipulate genes, create new organisms, or change the properties of existing living cells. This makes it possible to more extensively use the potential of organisms and facilitates human economic activity.

History of biotechnology

No matter how strange it may sound, biotechnology takes its origins from the distant past, when people were just beginning to engage in winemaking, baking and other methods of cooking. For example, the biotechnological process of fermentation, in which microorganisms actively participated, was known back in ancient Babylon, where it was widely used.

Biotechnology began to be considered as a science only at the beginning of the 20th century. Its founder was the French scientist, microbiologist Louis Pasteur, and the term itself was first introduced into use by the Hungarian engineer Karl Ereki (1917). The 20th century was marked by the rapid development of molecular biology and genetics, where the achievements of chemistry and physics were actively used. One of the key stages of the research was the development of methods for culturing living cells. Initially, only fungi and bacteria began to be grown for industrial purposes, but after several decades, scientists can create any cells, completely controlling their development.

At the beginning of the 20th century, the fermentation and microbiological industries actively developed. At this time, the first attempts were made to establish the production of antibiotics. The first food concentrates are being developed, and the level of enzymes in products of animal and plant origin is being monitored. In 1940, scientists managed to obtain the first antibiotic - penicillin. This became the impetus for the development of industrial production of drugs; an entire branch of the pharmaceutical industry emerged, which represents one of the cells of modern biotechnology.

Today, biotechnologies are used in the food industry, medicine, agriculture and many other areas of human activity. Accordingly, many new scientific directions with the prefix “bio” have appeared.

Bioengineering

When asked what biotechnology is, the majority of the population will no doubt answer that it is nothing more than genetic engineering. This is partly true, but engineering is only part of the broad discipline of biotechnology.

Bioengineering is a discipline whose main activity is aimed at improving human health by combining knowledge from the fields of engineering, medicine, biology and applying them in practice. The full name of this discipline is biomedical engineering. Her main specialization is solving medical problems. The use of biotechnology in medicine makes it possible to model, develop and study new substances, develop pharmaceuticals, and even save a person from congenital diseases that are transmitted through DNA. Specialists in this field can create devices and equipment to carry out new procedures. Thanks to the use of biotechnology in medicine, artificial joints, pacemakers, skin prostheses, and heart-lung machines have been developed. With the help of new computer technologies, bioengineers can create proteins with new properties using computer simulations.

Biomedicine and pharmacology

The development of biotechnology has made it possible to look at medicine in a new way. By developing a theoretical basis about the human body, specialists in this field have the opportunity to use nanotechnology to change biological systems. The development of biomedicine has given impetus to the emergence of nanomedicine, the main activity of which is to monitor, correct and design living systems at the molecular level. For example, targeted delivery of medicines. This is not a courier delivery from a pharmacy to your home, but a transfer of the drug directly to the diseased cell of the body.

Biopharmacology is also developing. It studies the effects that substances of biological or biotechnological origin have on the body. Research in this area of ​​knowledge focuses on the study of biopharmaceuticals and the development of methods for their creation. In biopharmacology, therapeutic agents are obtained from living biological systems or body tissues.

Bioinformatics and bionics

But biotechnology is not only the study of molecules of tissues and cells of living organisms, it is also the application of computer technology. Thus, bioinformatics takes place. It includes a set of approaches such as:

  • Genomic bioinformatics. That is, computer analysis methods that are used in comparative genomics.
  • Structural bioinformatics. Development of computer programs that predict the spatial structure of proteins.
  • Calculation. Creating computational methodologies that can control biological systems.

In this discipline, methods of mathematics, statistical computing and computer science are used together with biological methods. Just as in biology the techniques of computer science and mathematics are used, so in the exact sciences today they can use the doctrine of the organization of living organisms. Like in bionics. This is an applied science where the principles and structures of living nature are used in technical devices. We can say that this is a kind of symbiosis of biology and technology. Disciplinary approaches in bionics look at both biology and technology from a new perspective. Bionics looked at the similarities and differences between these disciplines. This discipline has three subtypes - biological, theoretical and technical. Biological bionics studies the processes that occur in biological systems. Theoretical bionics builds mathematical models of biosystems. And technical bionics applies the developments of theoretical bionics to solve various problems.

As you can see, the achievements of biotechnology are widespread in modern medicine and healthcare, but this is just the tip of the iceberg. As already mentioned, biotechnology began to develop from the moment a person began to prepare his own food, and after that it was widely used in agriculture for growing new breeding crops and breeding new breeds of domestic animals.

Cell engineering

One of the most important techniques in biotechnology is genetic and cell engineering, which focus on creating new cells. With the help of these tools, humanity has been able to create viable cells from completely different elements belonging to different species. Thus, a new set of genes that does not exist in nature is created. Genetic engineering makes it possible for a person to obtain the desired qualities from modified plant or animal cells.

The achievements of genetic engineering in agriculture are especially valued. This makes it possible to grow plants (or animals) with improved qualities, so-called selective species. Breeding activity is based on the selection of animals or plants with pronounced favorable traits. These organisms are then crossed and a hybrid is obtained with the required combination of useful traits. Of course, everything sounds simple in words, but getting the desired hybrid is quite difficult. In reality, it is possible to obtain an organism with only one or a few beneficial genes. That is, only a few additional qualities are added to the source material, but even this made it possible to make a huge step in the development of agriculture.

Selection and biotechnology have enabled farmers to increase yields, make fruits larger, tastier, and most importantly, resistant to frost. Selection does not bypass the livestock sector. Every year new breeds of domestic animals appear, which can provide more livestock and food.

Achievements

Scientists distinguish three waves in the creation of breeding plants:

  1. Late 80s. That's when scientists first began to breed plants that were resistant to viruses. To do this, they took one gene from species that could resist diseases, “transplanted” it into the DNA structure of other plants and made it “work.”
  2. Early 2000s. During this period, plants with new consumer properties began to be created. For example, with a high content of oils, vitamins, etc.
  3. Our days. In the next 10 years, scientists plan to bring to market vaccine plants, drug plants and biorecovery plants that will produce components for plastics, dyes, etc.

Even in animal husbandry, the promise of biotechnology is exciting. Animals have long been created that have a transgenic gene, that is, they possess some kind of functional hormone, for example growth hormone. But these were only initial experiments. Research has resulted in transgenic goats that can produce a protein that stops bleeding in patients suffering from poor blood clotting.

At the end of the 90s of the last century, American scientists began to work closely on cloning animal embryo cells. This would make it possible to grow livestock in test tubes, but for now this method still needs to be improved. But in xenotransplantation (transplantation of organs from one species to another), scientists in the field of applied biotechnology have achieved significant progress. For example, pigs with the human genome can be used as donors, then there is a minimal risk of rejection.

Food biotechnology

As already mentioned, biotechnological research methods were initially used in food production. Yoghurt, sourdough, beer, wine, bakery products are products obtained using food biotechnology. This segment of research involves processes aimed at changing, improving, or creating specific characteristics of living organisms, particularly bacteria. Specialists in this field of knowledge are developing new techniques for the production of various food products. They are looking for and improving mechanisms and methods for their preparation.

The food a person eats every day should be rich in vitamins, minerals and amino acids. However, as of today, according to the UN, there is a problem of providing people with food. Almost half the population does not have enough food, 500 million are hungry, and a quarter of the world's population eats insufficient quality food.

Today there are 7.5 billion people on the planet, and if action is not taken to improve the quality and quantity of food, if this is not done, people in developing countries will suffer devastating consequences. And if it is possible to replace lipids, minerals, vitamins, antioxidants with food biotechnology products, then it is almost impossible to replace protein. More than 14 million tons of protein each year are not enough to meet the needs of humanity. But this is where biotechnology comes to the rescue. Modern protein production is based on the artificial formation of protein fibers. They are impregnated with the necessary substances, given shape, the appropriate color and smell. This approach makes it possible to replace almost any protein. And the taste and appearance are no different from the natural product.

Cloning

An important area of ​​knowledge in modern biotechnology is cloning. For several decades now, scientists have been trying to create identical offspring without resorting to sexual reproduction. The cloning process should result in an organism that is similar to the parent not only in appearance, but also in genetic information.

In nature, the cloning process is common among some living organisms. If a person gives birth to identical twins, they can be considered natural clones.

Cloning was first carried out in 1997, when Dolly the sheep was artificially created. And already at the end of the twentieth century, scientists began to talk about the possibility of human cloning. In addition, the concept of partial cloning was explored. That is, it is possible to recreate not the whole organism, but its individual parts or tissues. If you improve this method, you can get an “ideal donor.” In addition, cloning will help preserve rare animal species or restore extinct populations.

Moral aspect

Although the fundamentals of biotechnology can have a decisive impact on the development of all humanity, this scientific approach is poorly received by the public. The overwhelming majority of modern religious leaders (and some scientists) are trying to warn biotechnologists against getting too carried away with their research. This is especially acute when it comes to issues of genetic engineering, cloning and artificial reproduction.

On the one hand, biotechnology seems to be a bright star, a dream and hope that will become reality in the new world. In the future, this science will give humanity many new opportunities. It will become possible to overcome fatal diseases, physical problems will be eliminated, and a person, sooner or later, will be able to achieve earthly immortality. Although, on the other hand, the gene pool may be affected by the constant consumption of genetically modified products or the appearance of people who were created artificially. The problem of changing social structures will arise, and it is likely that we will have to face the tragedy of medical fascism.

That's what biotechnology is. Science that can bring brilliant prospects to humanity by creating, changing or improving cells, living organisms and systems. She will be able to give a person a new body, and the dream of eternal life will become a reality. But you will have to pay a considerable price for this.

Biotechnology concept

Definition 1

Biotechnology is a science that studies the possibility of using living organisms or their metabolic products to solve technological problems.

With the help of biotechnology, certain needs are met, such as the development of medicines, the creation of new species of animals and plants or their modification, which allows increasing the quality of food products.

As a science, biotechnology originated in the early 70s of the twentieth century. The starting point was genetic engineering, when scientists were able to transfer genetic material from one organism to another without sexual processes, using recombinant DNA or RNA. This method is used to improve or change a specific organism.

Biotechnology in modern medicine

Biotechnologies used in medicine are divided into two groups:

  • diagnostic, which are chemical and physical
  • medicinal

Production processes in which biological objects or substances for medical purposes are created are also classified as medical. These could be vitamins. Enzymes, antibiotics, polysaccharides, amino acids.

In medicine, biotechnology is used to produce insulin, for which genetically modified bacteria are used. Biotechnology in medicine is also used to create erythropoietin.

Note 1

Erythropoietin is a hormone that stimulates the formation of red blood cells in the bone marrow.

Biotechnology in modern science

The use of biotechnology in modern science plays a vital role and brings enormous benefits. As a result of the discovery of genetic engineering, it became possible to develop new varieties of plants and animal breeds that would be very useful for agriculture.

The study of biotechnology is not exclusively associated with biological sciences. For example, biotechnology is used in microelectronics, where ion-selective transistors have been developed based on the field effect. Biotechnologies are also used to increase oil recovery from oil reservoirs. A particularly developed area of ​​​​use of biotechnologies is their use for the treatment of domestic and waste water. In addition to those listed, other scientific disciplines have also contributed to the development of biotechnology. Thus, biotechnology is classified as a complex science.

The lack of socio-economic needs is another reason for the active study of biotechnology. According to scientists, biotechnology can help solve problems such as:

  • shortage of fresh or purified water in some regions
  • environmental pollution by chemicals
  • lack of energy resources
  • the need for new environmentally friendly materials
  • improving the level of medicine, etc.

Modern biotechnologies: application in practice, ethical issues

Biotechnology is not only a science, but also a field of practical human activity, which is engaged in the production of various types of products using living cells or organisms.

Genetics is the theoretical basis of biotechnology. The practical basis of biotechnology is the microbiological industry. It, in turn, received active development after the discovery of antibiotics.

The objects of biotechnology are bacteria, viruses, fungi, as well as isolated cells and organelles.

The main areas of modern biotechnology are genetic and cellular engineering in combination with biochemistry.

Cellular engineering is the process of growing cells of various living organisms in specially created conditions, as well as research on them.

Plant cell engineering is the most successful area; it has made it possible to accelerate breeding processes, as a result of which the time for developing a new variety has been reduced from 11 to 3 years.

Definition 2

Genetic engineering is a field of molecular biology that studies the genes of living organisms, is engaged in isolating genes from cells, as well as manipulating them. Enzymes and vectors are the main tools of genetic engineering.

Cloning is the process of obtaining descendants that are completely identical to the prototype. The first experiments were carried out on plants; cloning took place vegetatively.

Bacterial cloning is a human-controlled process of artificial propagation of plants.

At the end of the twentieth century, scientists began to actively discuss the possibility of human cloning.

Genetic engineering conducts research on microorganisms and humans. She also studies diseases related to oncology and the immune system.

The potential opened up by biotechnology is enormous not only for science, but also for other areas of activity. The use of biotechnological methods has made it possible to mass produce all proteins.

In the future, it is expected that biotechnology will improve plants and animals. With the help of genetic engineering they will fight hereditary diseases.

Genetic engineering, being the main direction in biotechnology, accelerates the solution to the problem of the agricultural, energy, and food crises.

Note 2

Biotechnology has the greatest impact on medicine and pharmaceuticals. It is expected that in the future it will be possible to treat incurable diseases.

In modern biotechnology, the field of microbial synthesis of substances valuable to humans is actively developing. Another important area of ​​modern biotechnology is the production of environmentally friendly energy.

However, there are a number of problems associated with the ethical side of biotechnology research. After information about experiments on human embryos and attempts at cloning became public, heated discussions arose on this topic among scientists and ordinary people. Therefore, such studies are subject to strict regulation. Compliance with this regulation is mandatory for all scientists and researchers. Whether it is worth cloning a person is a complex question. On the one hand, this opens up new opportunities, but on the other, no scientist can predict the possible consequences with 100% certainty.

History of biotechnology

The term “biotechnology” was first used by the Hungarian engineer Karl Ereky in 1917.

Certain elements of biotechnology appeared quite a long time ago. Essentially, these were attempts to use individual cells (microorganisms) and some enzymes in industrial production to facilitate a number of chemical processes.

A huge contribution to the practical use of the achievements of biochemistry was made by Academician A. N. Bakh, who created an important applied branch of biochemistry - technical biochemistry. A. N. Bach and his students developed many recommendations for improving technologies for processing a wide variety of biochemical raw materials, improving technologies for baking, brewing, winemaking, tea and tobacco production, etc., as well as recommendations for increasing the yield of cultivated plants by managing them by biochemical processes.

All these studies, as well as the progress of the chemical and microbiological industries and the creation of new industrial biochemical production (tea, tobacco, etc.) were the most important prerequisites for the emergence of modern biotechnology.

In production terms, the microbiological industry became the basis of biotechnology in the process of its formation. During the post-war years, the microbiological industry acquired fundamentally new features: microorganisms began to be used not only as a means of increasing the intensity of biochemical processes, but also as miniature synthetic factories capable of synthesizing the most valuable and complex chemical compounds inside their cells. The turning point was associated with the discovery and start of production of antibiotics.

The use of enzymes - biological catalysts - is a very tempting thing. After all, in many of their properties, primarily activity and selectivity of action (specificity), they are much superior to chemical catalysts. Enzymes ensure the implementation of chemical reactions without high temperatures and pressures, and accelerate them millions and billions of times. Moreover, each enzyme catalyzes only one specific reaction.

Enzymes have been used in the food and confectionery industry for a long time: many of the first patents from the beginning of the century concerned the production of enzymes specifically for these purposes. However, the requirements for these drugs were not very high at that time - essentially, not pure enzymes were used in production, but various extracts or dilapidated and dried cells of yeast or lower fungi. Enzymes (or rather, preparations containing them) were also used in the textile industry for bleaching and processing yarn and cotton threads.

Possible methods of using mass culture of algae.

Biological catalysts can also be used without extracting them from living organisms, directly in bacterial cells, for example. This method, in fact, is the basis of any microbiological production, and it has been used for a long time.

It is much more tempting to use pure enzyme preparations and thus get rid of the side reactions that accompany the vital activity of microorganisms. The creation of production in which a biological catalyst is used in its pure form as a reagent promises very great benefits - manufacturability increases, productivity and purity of processes increase many thousands of times. But here a fundamental difficulty arises: many enzymes, after being removed from the cell, are very quickly inactivated and destroyed. There can be no talk of any repeated use.

Scientists have found a solution to the problem. In order to stabilize, or, as they say, immobilize enzymes, to make them stable, suitable for repeated, long-term industrial use, enzymes are attached using strong chemical bonds to insoluble or soluble carriers - ion-exchange polymers, polyorganosiloxanes, porous glass, polysaccharides, etc. etc. As a result, enzymes become stable and can be used repeatedly. (This idea was then transferred to microbiology - the idea arose to immobilize living cells. Sometimes it is very necessary that during the process of microbiological synthesis they do not pollute the environment, do not mix with the products they synthesize, and in general are more like chemical reagents. And such immobilized cells were created; they are successfully used, for example, in the synthesis of steroid hormones - valuable drugs).

The development of a method for increasing the stability of enzymes significantly expands the possibilities of their use. With the help of enzymes, it is possible, for example, to obtain sugar from plant waste, and this process will be economically viable. A pilot plant for the continuous production of sugar from fiber has already been created.

Immobilized enzymes are also used in medicine. Thus, in our country, an immobilized streptokinase drug has been developed for the treatment of cardiovascular diseases (the drug is called “streptodecase”). This drug can be injected into blood vessels to dissolve blood clots that have formed in them. A water-soluble polysaccharide matrix (the class of polysaccharides includes, as is known, starch and cellulose, the selected polymer carrier was close to them in structure), to which streptokinase is chemically “attached”, significantly increases the stability of the enzyme, reduces its toxicity and allergic effect and does not affect the activity or ability of the enzyme to dissolve blood clots.

Substrates for obtaining unicellular protein for different classes of microorganisms.

The creation of immobilized enzymes, the so-called engineering enzymology, is one of the new areas of biotechnology. Only the first successes have been achieved. But they significantly transformed applied microbiology, technical biochemistry and the enzyme industry. Firstly, in the microbiological industry, developments in the production of enzymes of various natures and properties have now become relevant. Secondly, new areas of production have emerged related to the production of immobilized enzymes. Thirdly, the creation of new enzyme preparations has opened up the possibility of organizing a number of new industries to obtain the necessary substances using biological catalysts.

Plasmids

The greatest successes have been achieved in the field of changing the genetic apparatus of bacteria. They have learned to introduce new genes into the bacterial genome using small circular DNA molecules - plasmids present in bacterial cells. The necessary genes are “glued” into the plasmids, and then such hybrid plasmids are added to a culture of bacteria, for example Escherichia coli. Some of these bacteria consume such plasmids entirely. After this, the plasmid begins to replicate in the cell, reproducing dozens of copies of itself in the E. coli cell, which ensure the synthesis of new proteins.

Genetic Engineering

Now even more ingenious methods have been created and are being created for introducing genes into the cell of prokaryotes (organisms that do not have a formed nucleus and chromosomal apparatus). Next in line is the development of methods for introducing new genes into eukaryotic cells, primarily higher plants and animal organisms.

But what has already been achieved allows us to do a lot in the practice of the national economy. Microbiological production capabilities have expanded significantly. Thanks to genetic engineering, the field of microbiological synthesis of various biologically active compounds, intermediates for synthesis, feed proteins and additives and other substances has become one of the most profitable sciences: investing in promising biotechnological research promises a high economic effect.

For breeding work, regardless of whether it is carried out using mutagenesis or the “DNA industry,” scientists must have numerous collections of microorganisms. But now even the isolation of a new strain of natural microorganisms, previously unknown to science, costs approximately $100 on the global “bacterial culture market.” And in order to obtain a good industrial strain using conventional breeding methods, it is sometimes necessary to spend millions.

Now there are ways to speed up and reduce the cost of these processes. For example, at the All-Union Research Institute of Genetics and Selection of Microorganisms of the Glavmicrobioprom, an industrial superproducer strain of a microorganism was obtained that synthesizes threonine, an essential amino acid that is found in insufficient quantities in the feed of farm animals. The addition of threonine to feed increases animal weight gain by kilograms, which nationwide translates into millions of rubles in profit, and most importantly, an increase in livestock meat production.

The institute's team of scientists, led by director V. G. Debabov, used the common Escherichia coli, a ubiquitous microorganism, as the basis for obtaining an industrial strain. First, mutant cells were obtained that were capable of accumulating excess threonine in the medium. Then genetic changes were induced in the cell, which led to increased biosynthesis of amino acids. In this way, it was possible to obtain a strain that produced threonine, but 10 times less than the amount that was required for reasons of profitability of production. Then genetic engineering methods were introduced. With their help, the “threonine gene dose” in the bacterial DNA molecule was increased. Moreover, the number of genes that determine the synthesis of threonine was increased several times in the DNA molecule of the cell: identical genes appeared to be strung one after another in the DNA molecule. Naturally, the biosynthesis of threonine increased proportionally and reached a level sufficient for industrial production.

True, after this the strain had to be further improved, and again genetically. First, in order to purify the bacterial culture from cells in which plasmids with the “threonine gene” disappeared during the process of culture propagation. To do this, a gene was “sewn into” the cells, containing an encoded signal for the “suicide” of cells in which there were no plasmids with the “threonine gene” after division. In this way, the cell culture self-purified itself from ballast microorganisms. Then a gene was introduced into the cells, thanks to which it could develop on sucrose (and not expensive glucose and fructose, as before) and produce record amounts of threonine.

Essentially, the resulting microorganism was no longer Escherichia coli: manipulations with its genetic apparatus led to the emergence of a fundamentally new organism, designed quite consciously and purposefully. And this complex multi-stage work, which has enormous practical significance, was carried out using new original methods of genetic engineering in a very short time - in just three years.

By 1981, in a number of institutes of the country, and above all at the Institute of Bioorganic Chemistry named after. M. M. Shemyakin of the USSR Academy of Sciences under the leadership of Academician Yu. A. Ovchinikov, even more impressive work was performed. These studies have now taken the form of clear long-term programs, according to which they are further developed by a number of academic and industry institutes. These studies were aimed at achieving a truly miracle - introducing a gene isolated from the human body into a bacterial cell.

The work was carried out with several genes at once: the gene responsible for the synthesis of the hormone insulin, the gene that ensures the formation of interferon, and the gene that controls the synthesis of growth hormone.

First of all, scientists set themselves the task of “teaching” bacteria to synthesize the most valuable medicine - the hormone insulin. Insulin is necessary to treat diabetes. This hormone must be administered to patients constantly, and its production in the traditional way (from the pancreas of slaughter cattle) is difficult and expensive. In addition, the molecules of pig or cattle insulin are different from the molecules of human insulin, and naturally their activity in the human body is lower than the activity of human insulin. In addition, insulin, although small in size, is still a protein, and antibodies to it accumulate in the human body over time: the body fights against foreign proteins and rejects them. Therefore, injected bovine or porcine insulin may begin to be irreversibly inactivated, neutralized by these antibodies, and as a result may disappear before it has time to have a therapeutic effect. To prevent this from happening, it is necessary to introduce into the body substances that prevent this process, but they themselves are not indifferent to the body.

Human insulin could be produced through chemical synthesis. But this synthesis is so complex and expensive that it was carried out only for experimental purposes, and the amounts of insulin obtained were insufficient even for one injection. It was, rather, a symbolic synthesis, proof that chemists can synthesize real protein in a test tube.

Taking all this into account, scientists have set themselves such a complex and very important task - to establish the biochemical production of human insulin. A gene was obtained that provides insulin synthesis. Using genetic engineering methods, this gene was introduced into a bacterial cell, which as a result acquired the ability to synthesize a human hormone.

Equally of great interest and no less (and perhaps more) importance was the work carried out at the same institute on introducing the gene responsible for the synthesis of human interferon into a bacterial cell using genetic engineering methods. (Interferon is a protein that plays an extremely important role in the body's fight against viral infections.) The interferon gene was also introduced into the E. coli cell. The created strains were distinguished by a high yield of interferon, which has a powerful antiviral effect. The first industrial batches of human interferon have now been obtained. The industrial production of interferon is a very important achievement, since it is assumed that interferon also has antitumor activity.

At the Institute of the USSR Academy of Sciences, work was carried out to create bacterial cells that produce somatotropin - human growth hormone. The gene for this hormone was isolated from the pituitary gland and, using genetic engineering methods, integrated into a more complex DNA molecule, which was then introduced into the genetic apparatus of the bacterium. As a result, the bacterium acquired the ability to synthesize human hormones. This bacterial culture, as well as the bacterial culture with the introduced insulin gene, is being tested for the industrial production of human hormones in microbiological production.

These are just a few examples of work on introducing genes from higher organisms into bacterial cells. There are many more similar interesting and promising works.

Here's another example. English biochemists isolated a fairly large protein (about 200 amino acid residues) - thaumatin - from the fruits of an African shrub. This protein turned out to be 100 thousand times sweeter than sucrose. Now all over the world they are thinking about creating sugar substitutes, which, when consumed in large quantities, are far from harmless to the body. Therefore, thaumatin, a natural product that does not require special toxicological tests, has attracted close attention: after all, its insignificant additions to confectionery products can simply eliminate the use of sugar. Scientists decided that it was easier and more profitable to obtain thaumatin not from a natural source, but by microbiological synthesis using bacteria into which the thaumatin gene was introduced. And this work was done by introducing this gene into the same E. coli. For now, the sugar substitute thaumatin (called talin) is produced from a natural source, but its microbiological production is not far off.

So far we have been talking about introducing genes into bacterial cells. But this does not mean that work is not being done to introduce artificial genes into higher organisms - plants and animals. There are not fewer, but much more attractive ideas here. The practical implementation of some of them will be of exceptional importance for humanity. Thus, it is known that higher plants cannot absorb atmospheric nitrogen: they obtain it from the soil in the form of inorganic salts or as a result of symbiosis with nodule bacteria. The implementation of the idea - introducing the genes of these bacteria into plants - could lead to radical revolutionary changes in agriculture.

What is the situation with the introduction of genes into the genetic apparatus of eukaryotes? The main difficulty here is that it is impossible to change the genotype of all cells of a multicellular organism. Therefore, hopes are pinned on the creation of genetic engineering methods designed to work with plant cell cultures and single-celled plants.

The introduction of synthetic genes into artificially cultivated cells can lead to the production of a modified plant: under certain conditions, isolated cells can turn into whole plants. And in such a plant the genes artificially introduced into the original cell must act and be inherited.

Here, in addition to the prospects for the successful use of genetic engineering methods, another advantage of biotechnology emerges - using the method of cellular biotechnology, millions of identical plants can be obtained from one plant, and not dozens, as when using seeds. Cellular technology does not require large areas, does not depend on weather conditions and is characterized by enormous productivity.

Soviet scientists are now exploring another way of introducing genes into plant cells - creating a symbiotic community, where they are trying to introduce cyanobacteria, which are capable of both photosynthesis and nitrogen fixation, into plant protoplasts (they lack a cellulose membrane).

There are also certain prospects in the field of using genetic engineering methods in working with animals; in any case, there is a fundamental possibility of transferring genetic material into animal cells. This is especially convincingly shown in hybridomas. A hybridoma is a cell formed from a lymphocyte that produces antibodies and a tumor cell capable of unlimited reproduction, and combines both of these properties. Using hybridomas, highly specific antibodies can be obtained. The hybridoma method is another biotechnological method for obtaining valuable proteins.

Space biotechnology During the implementation of manned flight programs in the former USSR, a scientific and technical potential in the field of space biotechnology was developed with the participation of the parent organizations of Rosaviakosmos, the Ministry of Medical Industry, the Russian Academy of Sciences and the Russian Academy of Medical Sciences, which created the hardware and methodological base necessary for carrying out biotechnological experiments in orbital flight conditions. Over a 15-year period A number of programs of biotechnological experiments have been carried out, their results have been introduced into technologies for the production of various biologically active substances (antibiotics, immunostimulants, etc.). Using space biotechnology methods, a number of new therapeutic and diagnostic drugs have been created. The accumulated experience has made it possible to determine the most promising directions for the development of space biotechnology: · obtaining high-quality crystals of biologically significant substances in order to determine their spatial structure and create new drugs for medicine, pharmacology, veterinary medicine, other sectors of the national economy and various fields of science; · obtaining and selecting in conditions microgravity of improved, as well as recombinant industrial strains of microorganisms, producers of biologically active substances for medicine, pharmacology, agriculture and ecology; electrophoretic separation of biological substances, in particular, fine high-performance purification of genetically engineered and viral proteins, mainly for medical purposes, as well as the isolation of specific cells characterized by the required secretory functions; · study of the influence of space flight factors on biological objects and physicochemical characteristics of biotechnological processes with with the aim of expanding fundamental knowledge in the field of biology and biotechnology. In 1989, RSC Energia named after. S.P. Korolev and RAO Biopreparat, having joined forces in research in one of the promising areas of space activity, created laboratories of space biotechnology. The scientific management of work in the field of biotechnology within the framework of the Russian national program at the Mir orbital station and the Russian segment of the international space station is carried out by the Chairman of the Space Biotechnology section of the KNTS of Rosaviakosmos and the Russian Academy of Sciences, Honored Scientist of the Russian Federation, Professor Yuri Tikhonovich Kalinin. Coordination of work, ensuring the creation and pre-flight preparation of on-board scientific equipment, biological materials during the implementation of biotechnological projects, as well as processing and analysis of the results obtained are carried out by specialized laboratories of space biotechnology at RAO Biopreparat (based on JSC Biokhimmash) and at RSC Energia. them. S.P. Queen. For the direct implementation of experiments on board orbital stations, a set of measures has been developed for their organization, support and support at all stages of implementation: · preparation of scientific experiments and equipment, training of crews together with the Russian State Research and Testing Center for Cosmonaut Training named after. Yu.A. Gagarin; · delivery of scientific equipment to the orbital complex; logistics support for experiments on board the orbital complex; planning, preparation and support of experiments at the Mission Control Center; return of the results of experiments from orbit and their delivery from the landing site to the laboratory. The above-mentioned space biotechnology laboratories have developed packages of documents necessary for the implementation of space experiments, including pre-flight preparation methods, passports and certificates, and other permitting documentation. We are ready, at the customer’s choice, to provide the necessary scientific advice in this area, as well as prepare and conduct space experiments with any biological objects. The prospects for obtaining high-quality crystals of biological substances in microgravity conditions, which we have repeatedly confirmed in commercial projects with foreign companies, are obvious. They made it possible to study with high accuracy the spatial structure of various biopolymers and use the results to create qualitatively new therapeutic, prophylactic and diagnostic drugs. Our experience in working with microbiological cultures of biodegradants of oil and petroleum products, as well as with strains used for plant protection products, cultures of higher cells plants, made it possible to obtain variants of crops after their exposure in space that are significantly more active than the original strains. Experiments on the recombination of microorganisms under orbital flight conditions showed the real possibility of 100% transfer of genetic material between distant species, which makes it possible to obtain unique hybrids with new specified properties. Numerous results of experiments conducted in microgravity conditions on electrophoretic purification and separation of protein and cellular biological objects confirmed the possibility and the effectiveness of using electrophoretic methods for the production of experimental and pilot-industrial batches of highly pure and highly homogeneous economically valuable biologically active substances. We are ready, based on your orders, using our or other equipment to carry out research on the crystallization of biological objects in space, obtaining improved or recombinant strains, as well as electrophoresis and other areas of research, both at your request and in cooperation. In our opinion, this is a very promising area , both scientifically and commercially, a project to create a universal installation for growing and obtaining crystalline proteins in space flight conditions can serve. A description of the project is attached. We will also consider any proposals from interested parties for the preparation and conduct of space biotechnological experiments, and we will carry out their examination feasibility and ensure the implementation of the proposed projects on a commercial basis. GOALS AND OBJECTIVES OF THE PROJECT The project is carried out through the efforts of RAO Biopreparat and potential participants interested in the development of advanced biotechnological scientific equipment and the production of competitive bioproducts in space flight conditions. The main goal of the project is to crystallize biological products in orbital flight conditions is the creation and operation on the International Space Station (ISS) of a new generation of biocrystallization equipment capable of obtaining large, homogeneous crystals of a wide range of biological objects, as well as the prompt receipt on Earth of video and telemetric information about the main parameters of the process and the results obtained. When organizing work within the project The following tasks are set: · development of mechanisms of interaction between the parties to the project on organizational, methodological, technical, scientific and economic issues; · on the basis of Russian biocrystallizers and foreign electronic and video equipment, produce prototypes and flight samples of biocrystallization equipment with characteristics exceeding known world analogues in terms of efficiency and reliability; · operate the created equipment on the ISS; both for individual national programs of the participating parties, and for joint scientific or commercial projects; · search for ways and means of implementing scientific results obtained during flight experiments based on the mutual interests of the project participants. BRIEF TECHNICAL CHARACTERISTICS OF THE EQUIPMENT Below are brief technical characteristics of the equipment for crystallization of biological objects, created on the basis of Russian developments. Universal biocrystallizer Functionally, the equipment is a set of universal crystallization cassettes that allow crystallization of proteins (or other biological objects) by various methods. The equipment provides: multi-level and highly reliable sealing of chambers with working solutions; rapid execution of operations for separate filling of crystallization cassette chambers with solutions of protein (or other biopolymer) and precipitant; implementation of several crystallization methods in one cassette; high reproducibility characteristics of the process in various crystallization cells of the universal cassette; high degree of interchangeability of the main functional elements of the biocrystallizer; · convenient and quick execution of operations of sterilization, assembly, leak testing and filling with working solutions; · convenient and non-destructive extraction of the resulting crystals; · high reliability and maintainability; · manual and automatic activation/deactivation of the crystallization process; · measurement and recording of the temperature of crystallization cassettes on all stages of transportation and operation; high utilization rate of payload mass at the stages of insertion into orbit and return to Earth; low demands on delivery and return vehicles; flexibility in constructing and using a scientific program with minimal ISS resources used; possibility of modular expansion of crystallization cells depending on customer requirements. Delivery on board the ISS and return to Earth of universal biocrystallizer cassettes is carried out in a thermally insulating return container (TRC) with an autonomous temperature recorder. COMPOSITION OF EQUIPMENT The complete configuration of the equipment has the following composition: · set of universal biocrystallizer cassettes - 12 pcs. (the configuration of the cassettes is determined by the director of the experiment); · thermally insulating returnable container (TRC) with an autonomous temperature recorder; · manual drive of the cassettes; · biotechnological universal thermostat (TBU) for active thermostating of cassettes in a semi-automatic mode; · electric drive unit for activation/deactivation of cassettes in the TCU; · electric drive control unit; · video monitoring system for crystallization cells in the TBU; · monitoring and control unit for the video monitoring system and interface (VIS) with the ISS TV system; · set of connecting cables. Each of the universal crystallization cassettes is structurally made monoblock. The cassette includes 4 autonomous crystallization cells. Each crystallization cell, in turn, has from one to three crystallization (protein) chambers and one or more chambers for the precipitant solution.

Biohydrometallurgy

This direction was previously known as Microbial leaching of metals from ores. Studies the extraction of metals from their ores using microorganisms. In the 50s and 60s it became clear that there are microorganisms capable of transferring metals from ore minerals into solution. The mechanisms for such translation are different. For example, some leaching microorganisms directly oxidize pyrite: 4FeS 2 + 15O 2 + 2H 2 O = 2Fe 2 (SO 4) 3 + 2H 2 SO 4

And the ferric ion serves as a strong oxidizing agent, capable of transferring copper from chalcocynite into solution: Cu 2 S + 2Fe 2 (SO 4) 3 = 2CuSO 4 + 4FeSO 4 + S or Uranium from uraninite: UO 2 + Fe 2 (SO 4) 3 = UO 2 SO 4 + 2FeSO 4

Oxidation reactions are exothermic; when they occur, energy is released that is used by microorganisms in the course of their life.

So what is the structure of biotechnology? Considering that biotechnology is actively developing and its structure has not been finally determined, we can only talk about those types of biotechnology that currently exist. This is cellular biotechnology - applied microbiology, plant and animal cell cultures (this was discussed when we talked about the microbiological industry, the possibilities of cell cultures, and chemical mutagenesis). These are genetic biotechnology and molecular biotechnology (they provide the “DNA industry”). And finally, this is the modeling of complex biological processes and systems, including engineering enzymology (we talked about this when we talked about immobilized enzymes).

It is clear that biotechnology has a huge future. And its further development is closely connected with the simultaneous development of all the most important branches of biological science that study living organisms at different levels of their organization. After all, no matter how biology differentiates, no matter what new scientific directions arise, the object of their research will always be living organisms, which are a set of material structures and diverse processes that make up a physical, chemical and biological unity. And this - the very nature of living things - predetermines the need for a comprehensive study of living organisms. Therefore, it is natural and natural that biotechnology arose as a result of the progress of a complex direction - physical and chemical biology and develops simultaneously and in parallel with this direction.

One of the main practical tasks of cell and tissue engineering has always been the creation of cultured in vitro cells of living equivalents of tissues and organs for the purpose of their use in replacement therapy to restore damaged structures and functions of the body. The greatest successes in this direction have been achieved using grown in vitro keratinocytes for the treatment of skin damage, and primarily in the treatment of burn wounds.

In conclusion, one more important circumstance should be noted that distinguishes biotechnology from other areas of science and production. It is initially focused on problems that worry modern humanity: food production (primarily protein), maintaining energy balance in nature (moving away from the focus on the use of irreplaceable resources in favor of renewable resources), environmental protection (biotechnology - “clean” production, which, however, requires a lot of water).

Thus, biotechnology is a natural result of the development of mankind, a sign of its achievement of an important, one might say turning point, stage of development.

Biotechnology industry

The biotechnology industry is sometimes divided into four areas:

  • "« Red "biotechnology" - production of biopharmaceuticals (proteins, enzymes, antibodies) for humans, as well as correction of the genetic code.
  • "« Green biotechnology - development and introduction into culture of genetically modified plants.
  • "« White "biotechnology" - production of biofuels, enzymes and biomaterials for various industries.
  • Academic and government research - for example, deciphering the rice genome.

"Microbiological industry" produces 150 types of products that are extremely necessary for the national economy. Its pride is feed protein obtained by growing yeast. More than 1 million tons are produced annually. Another important achievement is the release of the most valuable feed additive - the essential (that is, not formed in the animal’s body) amino acid lysine. The digestibility of protein substances contained in the products of microbiological synthesis is such that 1 ton of feed protein saves 5-8 tons of grain. Adding 1 ton of yeast biomass to the diet of poultry, for example, allows you to obtain an additional 1.5-2 tons of meat or 25-35 thousand eggs, and in pig farming it frees up 5-7 tons of feed grain. Yeast is not the only possible source of protein. It can be obtained by growing microscopic green algae, various protozoa and other microorganisms. Technologies for their use have already been developed, giant enterprises with a capacity of 50 to 300 thousand tons of products per year are being designed and built. Their operation will make it possible to make a significant contribution to solving national economic problems.

If a human gene responsible for the synthesis of an enzyme or other substance important for the body is transplanted into the cells of microorganisms, then under appropriate conditions the microorganisms will produce a compound alien to them on an industrial scale. Scientists have developed and put into production a method for producing human interferon that is effective in the treatment of many viral diseases. The same amount of interferon is extracted from 1 liter of culture fluid as was previously obtained from many tons of donor blood. Savings from the introduction of the new method amount to 200 million rubles per year.

Another example is the production of human growth hormone using microorganisms. Joint developments by scientists from the Institute of Molecular Biology, the Institute of Molecular Biology, the Institute of Biochemistry and Physiology of Microorganisms of Russia and Russian institutes make it possible to produce grams of the hormone, whereas previously this drug was obtained in milligrams. The drug is currently being tested. Genetic engineering methods have created the possibility of obtaining vaccines against such dangerous infections as hepatitis B, foot and mouth disease in cattle, as well as developing methods for the early diagnosis of a number of hereditary diseases and various viral infections.

Genetic engineering begins to actively influence the development of not only medicine, but also other areas of the national economy. The successful development of genetic engineering methods opens up broad opportunities for solving a number of problems facing agriculture. This includes the creation of new valuable varieties of agricultural plants that are resistant to various diseases and adverse environmental factors, and the acceleration of the selection process when breeding highly productive animal breeds, and the creation of highly effective diagnostic tools and vaccines for veterinary medicine, and the development of methods for biological nitrogen fixation. The solution to these problems will contribute to the scientific and technological progress of agriculture, and a key role in this will belong to the methods of genetic, and also, obviously, cellular engineering.

Cell engineering - an unusually promising direction of modern biotechnology. Scientists have developed methods for growing animal and even human plant cells under artificial conditions (cultivation). Cell cultivation makes it possible to obtain various valuable products that were previously obtained in very limited quantities due to the lack of sources of raw materials. Plant cell engineering is developing particularly successfully. Using genetic methods, it is possible to select lines of such plant cells - producers of practically important substances, which are able to grow on simple nutrient media and at the same time accumulate valuable products several times more than the plant itself. Cultivation of plant cell masses is already used on an industrial scale to produce physiologically active compounds. For example, the production of ginseng biomass has been established for the needs of the perfume and medical industries. The foundations are being laid for the production of biomass from medicinal plants - Dioscorea and Rauwolfia. Methods are being developed for growing the cell mass of other rare plants that produce valuable substances (Rhodiola rosea, etc.). Another important area of ​​cell engineering is clonal micropropagation of plants based on tissue culture. This method is based on an amazing property of plants: from a single cell or piece of tissue, under certain conditions, a whole plant can grow, capable of normal growth and reproduction. Using this method, up to 1 million plants per year can be obtained from a small part of a plant. Clonal micropropagation is used for the improvement and rapid propagation of rare, economically valuable or newly created varieties of agricultural crops. In this way, healthy plants of potatoes, grapes, sugar beets, garden strawberries, raspberries and many other crops are obtained from cells not infected with viruses. Currently, methods have been developed for micropropagation of more complex objects - woody plants (apple trees, spruce trees, pine trees). Based on these methods, technologies for the industrial production of initial planting material of valuable tree species will be created. Cellular engineering methods will significantly speed up the selection process when developing new varieties of cereals and other important agricultural crops: the period for obtaining them is reduced to 3-4 years (instead of 10-12 years required when using conventional breeding methods). A fundamentally new method of cell fusion, developed by scientists, is also a promising way to develop new varieties of valuable agricultural crops. This method makes it possible to obtain hybrids that cannot be created by conventional crossing due to the barrier of interspecific incompatibility. Using the cell fusion method, for example, hybrids of various types of potatoes, tomatoes, and tobacco were obtained; tobacco and potatoes, rapeseed and turnips, tobacco and belladonna. New varieties are being created based on a hybrid of cultivated and wild potatoes that is resistant to viruses and other diseases. Valuable breeding material for tomatoes and other crops is obtained in a similar way. In the future, the integrated use of genetic and cellular engineering methods to create new varieties of plants with predetermined properties, for example, with systems designed for fixing atmospheric nitrogen. Great strides have been made in cell engineering in the field of immunology: methods have been developed for producing special hybrid cells that produce individual, or monoclonal, antibodies. This made it possible to create highly sensitive diagnostic tools for a number of serious diseases of humans, animals and plants. Modern biotechnology makes a significant contribution to solving such an important problem as the fight against viral diseases of agricultural crops, which cause great damage to the national economy. Scientists have developed highly specific sera to detect more than 20 viruses that cause diseases in various crops. A system of instruments and devices for mass automatic express diagnostics of viral plant diseases in agricultural production conditions has been developed and manufactured. New diagnostic methods make it possible to select virus-free starting material (seeds, tubers, etc.) for planting, which contributes to a significant increase in yield. Work on engineering enzymology is of great practical importance. Its first important success was the immobilization of enzymes - the fixation of enzyme molecules using strong chemical bonds on synthetic polymers, polysaccharides and other matrix carriers. Fixed enzymes are more stable and can be used repeatedly. Immobilization allows for continuous catalytic processes, obtaining products that are not contaminated with enzymes (which is especially important in a number of food and pharmaceutical industries), and significantly reducing its cost. This method is used, for example, to obtain antibiotics. Thus, scientists have developed and introduced into industrial production a technology for producing antibiotics based on the immobilized enzyme penicillin amidase. As a result of the use of this technology, the consumption of raw materials decreased five times, the cost of the final product decreased by almost half, the production volume increased seven times, and the total economic effect amounted to about 100 million rubles. The next step in engineering enzymology was the development of methods for immobilizing microbial cells, and then plant and animal cells. Immobilized cells are the most economical biocatalysts, as they have high activity and stability, and most importantly, their use completely eliminates the cost of isolating and purifying enzymes. Currently, based on immobilized cells, methods have been developed for the production of organic acids, amino acids, antibiotics, steroids, alcohols and other valuable products. Immobilized cells of microorganisms are also used for wastewater treatment, processing of agricultural and industrial waste. Biotechnology is increasingly used in many branches of industrial production: methods have been developed for using microorganisms to extract non-ferrous precious metals from ores and industrial waste, to increase oil recovery, and to combat methane in coal mines. Thus, to free mines from methane, scientists proposed drilling wells in coal seams and feeding them a suspension of methane-oxidizing bacteria. In this way, it is possible to remove about 60% of methane even before the formation begins to be exploited. And recently they found a simpler and more effective method: a suspension of bacteria is sprayed on the rocks of the goaf, from where gas is most intensely released. Spraying the suspension can be done using special nozzles installed on the supports. Tests that were carried out in the mines of Donbass showed that microscopic “workers” quickly destroy from 50 to 80% of the dangerous gas in the workings. But with the help of other bacteria that themselves release methane, it is possible to increase the pressure in oil reservoirs and ensure more complete oil extraction. Biotechnology will also have to make a significant contribution to solving the energy problem. Limited oil and gas reserves force us to look for ways to use unconventional energy sources. One of these ways is the bioconversion of plant raw materials, or, in other words, the enzymatic processing of cellulose-containing industrial and agricultural waste. As a result of bioconversion, glucose can be obtained, and from it alcohol, which will serve as fuel. Research on the production of biogas (mainly methane) by processing livestock, industrial and municipal waste with the help of microorganisms is increasingly being developed. At the same time, the residues after processing are highly effective organic fertilizers. Thus, several problems are solved in this way: protecting the environment from pollution, obtaining energy and producing fertilizers. Biogas production plants are already operating in different countries. The possibilities of biotechnology are almost limitless. It boldly invades various spheres of the national economy. And in the near future, undoubtedly, the practical significance of biotechnology in solving the most important problems of breeding, medicine, energy, and environmental protection from pollution will increase even more.

Transgenic plants

Transgenic plants are those plants to which genes have been transplanted.

  • 1. Potatoes resistant to the Colorado potato beetle were created by introducing a gene isolated from the DNA of a cell of the soil Thuringian bacillus, which produces a protein that is poisonous to the Colorado potato beetle (poison is produced in the stomach of the beetle, but not in humans). They used an intermediary - Escherichia coli cells. Potato leaves began to produce a protein that is poisonous to beetles.
  • 2. Uses products from transgenic soybeans, corn, potatoes and sunflowers.
  • 3. In America they decided to grow a frost-resistant tomato. They took a flounder gene responsible for thermoregulation and transplanted it into tomato cells. But the tomato understood this information in its own way; it did not stop being afraid of frost, but stopped deteriorating during storage. It can lie in a room for six months and not rot.

Transgenic animals

Transgenic animals, experimentally obtained animals containing in all cells of their body additional integrated with chromosomes and expressed foreign DNA (transgene), which is inherited according to Mendelian laws.

Rarely, a transgene can replicate and be inherited as an extrachromosomal autonomously replicating DNA fragment. The term “transgenosis” was proposed in 1973 to denote the transfer of genes from one organism to the cells of organisms of other species, including those that are distant in evolutionary terms. Transgenic animals are produced by transferring cloned genes (DNA) into the nuclei of fertilized eggs (zygotes) or embryonic stem (pluripotent) cells. Then, modified zygotes or eggs, in which their own nucleus is replaced with a modified nucleus of embryonic stem cells, or blastocysts (embryos) containing foreign DNA of embryonic stem cells are transplanted into the reproductive organs of the recipient female. There are isolated reports of the use of sperm to create transgenic animals, but this technique has not yet become widespread.

The first transgenic animals were obtained in 1974 in Cambridge (USA) by Rudolf Jaenisch as a result of injection of DNA from the monkey virus SV40 into a mouse embryo. In 1980, American scientist Georges Gordon and co-authors proposed using microinjection of DNA into the pronucleus of the zygote to create transgenic animals. It was this approach that laid the foundation for the widespread use of technology for producing transgenic animals. The first transgenic animals appeared in Russia in 1982. Using microinjections into the pronucleus of the zygote, the first transgenic farm animals (rabbit, sheep, pig) were obtained in the USA in 1985. Currently, to create transgenic animals, in addition to microinjections, other experimental techniques are used: infection of cells with recombinant viruses, electroporation, “targeting” cells with metal particles coated with recombinant DNA on their surface.

In recent years, the advent of animal cloning technology has created additional opportunities to create transgenic animals. There are already transgenic animals obtained by microinjecting genes into the nuclei of differentiated cells.

All available methods of gene transfer are not yet very effective. To obtain one transgenic animal, on average, DNA microinjections are required into 40 mouse zygotes, 90 goat zygotes, 100 pig zygotes, 110 sheep zygotes and 1600 cow zygotes. The mechanisms of integration of exogenous DNA or the formation of autonomous replicons (replication units other than chromosomes) during transgenosis are not known. The integration of transgenes in each newly obtained transgenic animal occurs in random sections of chromosomes, and the integration of either a single copy of the transgene or multiple copies, usually located tandemly in a single locus of one of the chromosomes, can occur. As a rule, there is no homology between the site (location) of transgene integration and the transgene itself. When embryonic stem cells are used for transgenosis, preliminary selection is possible, which makes it possible to obtain transgenic animals with a transgene integrated as a result of homologous recombination with a certain region of the host genome. Using this approach, in particular, a targeted termination of the expression of a specific gene is carried out (this is called “gene knockout”).

The technology of creating transgenic animals is one of the most rapidly developing biotechnologies in the last 10 years. Transgenic animals are widely used both to solve a large number of theoretical problems and for practical purposes in biomedicine and agriculture. Some scientific problems could not be solved without the creation of transgenic animals. Using transgenic laboratory animal models, extensive research is being conducted to study the function of various genes, the regulation of their expression, the phenotypic manifestation of genes, insertional mutagenesis, etc. Transgenic animals are important for various biomedical studies. There are many transgenic animals that model various human diseases (cancer, atherosclerosis, obesity, etc.). Thus, the production of transgenic pigs with altered expression of genes that determine organ rejection will make it possible to use these animals for xenotransplantation (transplantation of pig organs to humans). For practical purposes, transgenic animals are used by various foreign companies as commercial bioreactors that ensure the production of various medical products (antibiotics, blood clotting factors, etc.). In addition, the transfer of new genes makes it possible to obtain transgenic animals that are characterized by increased productive properties (for example, increased wool growth in sheep, decreased fat content in pigs, changes in the properties of milk) or resistance to various diseases caused by viruses and other pathogens. Currently, humanity already uses many products obtained with the help of transgenic animals: medicines, organs, food.

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Biotechnology- a discipline that studies the possibilities of using living organisms, their systems or products of their vital activity to solve technological problems, as well as the possibility of creating living organisms with the necessary properties using genetic engineering.

Biotechnology is often referred to as the application of genetic engineering in the 21st century, but the term also refers to a broader set of processes for modifying biological organisms to meet human needs, starting with the modification of plants and animals through artificial selection and hybridization. With the help of modern methods, traditional biotechnological production has the opportunity to improve the quality of food products and increase the productivity of living organisms.

Before 1971, the term "biotechnology" was used primarily in the food and agricultural industries. Since the 1970s, scientists have used the term to refer to laboratory techniques, such as the use of recombinant DNA and cell cultures grown in vitro.

Biotechnology is based on genetics, molecular biology, biochemistry, embryology and cell biology, as well as applied disciplines - chemical and information technologies and robotics.

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History of biotechnology

The term “biotechnology” was first used by the Hungarian engineer Karl Ereky in 1917.

The use of microorganisms or their enzymes in industrial production, which ensure the technological process, has been known since ancient times, but systematic scientific research has significantly expanded the arsenal of methods and means of biotechnology.

Nanomedicine

Monitoring, correcting, engineering and controlling human biological systems at the molecular level using nanodevices and nanostructures. A number of technologies for the nanomedicine industry have already been created in the world. These include targeted delivery of drugs to diseased cells, laboratories on a chip, and new bactericidal agents.

Biopharmacology

Bionics

Artificial selection

Educational Biotechnology

Main article: Orange biotechnology

Orange biotechnology or educational biotechnology is used for the dissemination of biotechnology and training in this field. She develops interdisciplinary materials and educational strategies related to biotechnology (eg, recombinant protein production) accessible to the entire community, including people with special needs such as hearing impairment and/or visual impairment.

Hybridization

The process of forming or producing hybrids, which is based on the combination of genetic material from different cells in one cell. It can be carried out within one species (intraspecific hybridization) and between different systematic groups (distant hybridization, in which different genomes are combined). The first generation of hybrids is often characterized by heterosis, which is expressed in better adaptability, greater fertility and viability of organisms. With distant hybridization, the hybrids are often sterile.

Genetic Engineering

Green glowing pigs are transgenic pigs bred by a group of researchers from National Taiwan University by introducing a green fluorescent protein gene into the DNA of the embryo, borrowed from a fluorescent jellyfish. Aequorea victoria. The embryo was then implanted into the uterus of a female pig. Piglets glow green in the dark and have a greenish tint to their skin and eyes in daylight. The main purpose of breeding such pigs, according to the researchers, is the ability to visually monitor tissue development during stem cell transplantation.

Biotechnology – the medicine of the future

The new issue of the journal “SCIENCE from First Hands” was published “on the heels” of the all-Russian conference with international participation “Biotechnology - Medicine of the Future”, held in Novosibirsk Akademgorodok in July 2017. Among the organizers of the scientific forum are the Institute of Chemical Biology and Fundamental Medicine and the Institute of Cytology and genetics of the SB RAS, as well as the Novosibirsk National Research State University, where biomedical research is carried out within the framework of the strategic academic unit “Synthetic Biology”, which unites a number of Russian and foreign participants, primarily institutes of the SB RAS of biological profile. In the first, introductory article of the issue, its authors provide an overview of the most current directions and promising results of research related to the development and implementation of new genetic engineering, cellular, tissue, immunobiological and digital technologies in practical medicine, some of which are presented in detail in other articles of the issue

The rapid development of biological science, due to the emergence of high-performance devices and the creation of methods for manipulating information biopolymers and cells, has prepared the foundation for the development of future medicine. As a result of recent research, effective diagnostic methods have been developed, and opportunities have emerged for the rational design of antiviral, antibacterial and antitumor drugs, gene therapy and genome editing. Modern biomedical technologies are increasingly beginning to influence the economy and determine the quality of people's lives.

To date, the structure and functions of basic biological molecules have been studied in detail and methods for the synthesis of proteins and nucleic acids have been developed. These biopolymers by their nature are “smart” materials, as they are able to highly specifically “recognize” and act on certain biological targets. By targeted “programming” of such macromolecules, it is possible to create receptor molecular constructs for analytical systems, as well as drugs that selectively affect specific genetic programs or proteins.

“Smart drugs” created using synthetic biology methods open up opportunities for targeted(targeted) therapy of autoimmune, oncological, hereditary and infectious diseases. This gives grounds to talk about the introduction of personalized medicine approaches into medical practice, focused on the treatment of a specific person.

With the help of modern medical technologies and pharmaceuticals, today it is possible to cure many diseases that in the past represented a huge medical problem. But with the development of practical medicine and an increase in life expectancy, the task of healthcare in the truest sense of the word is becoming increasingly urgent: not just to fight diseases, but to maintain existing health so that a person can lead an active lifestyle and remain a full-fledged member of society until old age.

CHEERS! Modern genomic sequencing methods are being widely introduced into medicine, and in the near future all patients will have genetic passports. Information about the patient’s hereditary characteristics is the basis of prognostic personalized medicine. Forewarned is known to be forearmed. A person who is aware of the possible risks can organize his life in such a way as to prevent the development of the disease. This applies to lifestyle, food choices and therapeutic medications.
Provided that you constantly monitor a set of markers that signal deviations in the body’s functioning, you can correct them in a timely manner. There are already many methods for monitoring the state of the body: for example, using sensors that monitor the functioning of the cardiovascular system and the quality of sleep or devices that analyze gaseous products in the air exhaled by a person. Huge opportunities are opening up due to the development of minimally invasive liquid biopsy technologies and technologies for analyzing proteins and peptides circulating in the bloodstream. In the early stages of the disease, in many cases, the body’s condition can be corrected using “soft” methods: changing the nature of nutrition, using additional microelements, vitamins and probiotics. Recently, special attention has been paid to the possibilities of correcting deviations in the composition of the human intestinal microflora, which are associated with the development of a large number of pathological conditions.

This problem can be solved by ensuring constant effective control over the state of the body, which would allow one to avoid the effects of unfavorable factors and prevent the development of the disease, identifying the pathological process at a very early stage, and eliminating the very cause of the disease.

In this sense, the main task of future medicine can be formulated as “health management.” It is quite possible to do this if you have complete information about a person’s heredity and monitor key indicators of the body’s condition.

"Smart" diagnostics

To manage health, it is necessary to have effective and simple minimally invasive methods for early diagnosis of diseases and determination of individual sensitivity to therapeutic drugs, as well as environmental factors. For example, problems such as the creation of systems for gene diagnostics and identification of pathogens of human infectious diseases, and the development of methods for the quantitative determination of proteins and nucleic acids—disease markers—must be solved (and are already being solved).

Separately, it is worth highlighting the creation of methods for early non-invasive diagnostics ( liquid biopsy) tumor diseases based on the analysis of extracellular DNA and RNA. The source of such nucleic acids are both dead and living cells. Normally, their concentration is relatively low, but usually increases with stress and the development of pathological processes. When a malignant tumor occurs, nucleic acids secreted by cancer cells enter the bloodstream, and such characteristic circulating RNA and DNA can serve as markers of the disease.

Now, based on such markers, approaches to the early diagnosis of cancer, methods for predicting the risk of its development, as well as assessing the severity of the disease and the effectiveness of therapy are being developed. For example, at the Institute of Chemical Biology and Fundamental Medicine of the SB RAS it was shown that in prostate cancer the degree of methylation certain sections of DNA. A method has been developed to isolate circulating DNA from blood samples and analyze its methylation patterns. This method could become the basis for accurate non-invasive diagnosis of prostate cancer, which does not exist today.

An important source of information about health status can be the so-called non-coding RNAs, i.e. those RNAs that are not a template for protein synthesis. In recent years, it has been established that many different non-coding RNAs are formed in cells, which are involved in the regulation of a variety of processes at the level of cells and the whole organism. Studying the spectrum of microRNAs and long non-coding RNAs in various conditions opens up broad opportunities for fast and effective diagnosis. At the Institute of Molecular and Cell Biology SB RAS (IMBB SB RAS, Novosibirsk) and ICBFM SB RAS, a number of microRNAs have been identified as promising markers of tumor diseases.

RECOGNIZE THE ENEMY IN THE FACE Modern technologies using biological microchips make it possible to quickly and effectively identify the causative agents of a number of diseases (tuberculosis, AIDS, hepatitis B and C, anthrax, infections of newborns), detect the presence of certain biotoxins, determine chromosomal translocations in leukemia, register protein markers of cancer, and determine genetic predisposition to diseases and individual sensitivity to certain types of therapy. Technologies can also be used for genetic identification of individuals during forensic genetic examinations and the formation of DNA databases.
IBFM SB RAS participated in the implementation of two large international projects on the development of oligonucleotide microarrays, funded by the American Biotechnology Cooperation Program of the US Department of Health ( Biotechnology Engagement Program, US Department of Health and Human Services BTEP/DHHS). As part of the first project with the participation of IMB specialists. V. A. Engelhardt created microchips that make it possible to accurately identify various strains of smallpox and herpes viruses. Two microchip designs were developed (on a glass substrate and with gel spots), as well as a portable fluorescent detector for their analysis. As part of the second project, a universal microchip was created for typing the influenza A virus, which makes it possible to reliably distinguish 30 subtypes of this virus based on the determination of two surface proteins of the virus - hemagglutinin and neuraminidase

Using modern RNA and DNA sequencing technologies, a platform can be created for the diagnosis and prognosis of human cancer based on the analysis of microRNA content and genotyping, i.e., identifying specific genetic variants of a particular gene, as well as determining profiles expression(activity) of genes. This approach assumes the ability to quickly and simultaneously carry out multiple analyzes using modern devices – ​ biological microchips.

Biochips are miniature devices for parallel analysis of specific biological macromolecules. The idea of ​​​​creating such devices was born at the Institute of Molecular Biology named after. V. A. Engelhardt of the Russian Academy of Sciences (Moscow) back in the late 1980s. In a short time, biochip technologies have emerged as an independent field of analysis with a huge range of practical applications, from studying fundamental problems of molecular biology and molecular evolution to identifying drug-resistant strains of bacteria.

Today, the IMB RAS produces and uses in medical practice original test systems for identifying pathogens of a number of socially significant infections, including tuberculosis, while simultaneously identifying their resistance to antimicrobial drugs; test systems for assessing individual tolerability of cytostatic drugs and much more.

The world leader in biochip construction is an American company Affymetrix Inc. – ​produces biochips with a high density of molecular probes, based on photolithographic technologies used to produce semiconductor chips. On one such chip, in an area of ​​less than 2 cm 2, millions of spot points several microns in size can be located. Each such point contains several million identical oligonucleotides covalently bound to the surface of the microchip

The development of bioanalytical diagnostic methods requires constant improvement sensitivity– ​the ability to provide a reliable signal when registering small quantities of the detected substance. Biosensors– ​this is a new generation of devices that allow specific analysis of the content of various disease markers in samples of complex composition, which is especially important when diagnosing diseases.

IBFM SB RAS in collaboration with the Novosibirsk Institute of Semiconductor Physics SB RAS is developing microbiosensors based on field effect transistors, which are among the most sensitive analytical devices. Such a biosensor allows real-time monitoring of the interaction of biomolecules. Its constituent part is one of these interacting molecules, which plays the role of a molecular probe. The probe captures a molecular target from the analyzed solution, the presence of which can be used to judge the specific characteristics of the patient’s health.

"Complementary" medicine

Decoding the genomes of humans and pathogens of various infections has opened the way for the development of radical approaches to the treatment of diseases by targeting their root cause - the genetic programs responsible for the development of pathological processes. A deep understanding of the mechanism of disease in which nucleic acids are involved makes it possible to design therapeutic nucleic acids that restore a lost function or block the resulting pathology.

Double-stranded molecules of nucleic acids, DNA and RNA, are formed due to the interaction of pairs of nucleotides capable of mutual recognition and the formation of complexes due to the formation of hydrogen bonds. This property is called "complementarity"

Such an effect can be carried out using fragments of nucleic acids - ​synthetic oligonucleotides, capable of selectively interacting with certain nucleotide sequences in target genes according to the principle complementarity. The very idea of ​​using oligonucleotides for targeted effects on genes was first put forward in the laboratory of natural polymers (later the Department of Biochemistry) of the Novosibirsk Institute of Bioorganic Chemistry SB RAS (now the Institute of Chemical Biology and Fundamental Medicine SB RAS). The first drugs were created in Novosibirsk gene-targeted for selective inactivation of viral and some cellular RNAs.

Similar gene-targeted therapeutic drugs are now being actively developed based on nucleic acids, their analogs and conjugates (antisense oligonucleotides, interfering RNA, aptamers, genome editing systems). Research in recent years has shown that, based on antisense oligonucleotides it is possible to obtain a wide range of biologically active substances that act on various genetic structures and trigger processes leading to temporary “switching off” of genes or changes in genetic programs - ​the appearance mutations. It has been proven that with the help of such compounds it is possible to suppress the functioning of certain messenger RNA living cells, affecting protein synthesis, and also protect cells from viral infection.

“CURE” PROTEIN Regulation of gene expression under the influence of “antisense” oligonucleotides is possible at various levels. Thus, oligonucleotides complementary to the messenger RNA sequences suppress gene expression at the stage of translation, i.e., protein synthesis. But therapeutic nucleic acids can also interfere with other molecular biological processes, for example, correcting splicing disorders during mRNA maturation. In one of these disorders, the “wrong” dystrophin protein is synthesized in cells, which is an important structural component of muscle tissue. This leads to the development of a serious disease - Duchenne muscular dystrophy. The ICBFM SB RAS has developed therapeutic oligonucleotides for the treatment of this disease, and an application for a corresponding patent has already been filed.

Today, antisense oligonucleotides and RNAs that suppress the functions of mRNA and viral RNAs are used not only in biological research. Tests are underway on a number of antiviral and anti-inflammatory drugs created on the basis of artificial analogues of oligonucleotides, and some of them are already beginning to be introduced into clinical practice.

The Laboratory of Biomedical Chemistry of the Institute of Biomedical Medicine SB RAS, working in this direction, was created in 2013 thanks to a scientific mega-grant from the Government of the Russian Federation. Its organizer was Yale University professor, Nobel laureate S. Altman. The laboratory is conducting research into the physicochemical and biological properties of new promising artificial oligonucleotides, on the basis of which RNA-targeted antibacterial and antiviral drugs are being developed.

As part of the project led by S. Altman, a large-scale systematic study was carried out on the effects of various artificial analogs of oligonucleotides on pathogenic microorganisms: Pseudomonas aeruginosa, Salmonella, Staphylococcus aureus, and influenza virus. Target genes have been identified that can most effectively suppress these pathogens; The technological and therapeutic characteristics of the most active oligonucleotide analogues, including those exhibiting antibacterial and antiviral activity, are being assessed.

At the ICBFM SB RAS, for the first time in the world, they synthesized phosphorylguanidine oligonucleotide derivatives. These new compounds are electrically neutral, stable in biological environments, and bind strongly to RNA and DNA targets under a wide range of conditions. Due to their range of unique properties, they are promising for use as therapeutic agents, and can also be used to improve the efficiency of diagnostic tools based on biochip technologies.

Among commercial companies, the leader in the creation of therapeutic nucleic acids is an American company Ionis Pharmaceuticals, Inc.. (USA). After many years of clinical research, antisense drugs were introduced into medical practice: Kynamro– ​reduces the level of “bad” cholesterol, Alicaforsen– ​for the treatment of ulcerative colitis and Spinraza– ​for the treatment of Duchenne dystrophy. Drugs Ionis Clinical trials are underway against a number of other diseases. Leader in the creation of therapeutic interfering RNA – ​company Alnylam Pharmaceuticals– ​also conducts clinical trials of a whole series of drugs for the treatment of serious diseases (such as hereditary amyloidosis, severe forms of hypercholesterolemia, hemophilia), for which there are currently no effective treatments

Antisense effects on messenger RNAs are not limited to simple blocking splicing(the process of RNA “maturation”) or protein synthesis. More effective is enzymatic cutting of mRNA, provoked by the binding of a therapeutic oligonucleotide to the target. In this case, the oligonucleotide, a cleavage inducer, can subsequently contact another RNA molecule and repeat its action. The ICBFM SB RAS studied the effect of oligonucleotides that, when bound to mRNA, form complexes that can serve as substrates for the enzyme RNase P. This enzyme itself is RNA with catalytic properties ( ribozyme).

Not only antisense nucleotides, but also double-stranded RNA, acting according to the mechanism, turned out to be an extremely powerful means of suppressing gene activity RNA interference. The essence of this phenomenon is that, upon entering the cell, long dsRNAs are cut into short fragments (the so-called small interfering RNA, siRNA), complementary to a certain region of the messenger RNA. By binding to such mRNA, siRNAs trigger the action of an enzymatic mechanism that destroys the target molecule.

The use of this mechanism opens up new opportunities for creating a wide range of highly effective non-toxic drugs to suppress the expression of almost any, including viral, genes. At the ICBFM SB RAS, promising antitumor drugs have been designed based on small interfering RNAs, which have shown good results in animal experiments. One of the interesting findings is double-stranded RNA of an original structure, which stimulates the production of interferon, effectively suppressing the process of tumor metastasis. Good penetration of the drug into cells is ensured by new cationic carriers. liposomes(lipid vesicles), developed jointly with specialists from the Moscow State University of Fine Chemical Technologies named after M.V. Lomonosov.

New roles of nucleic acids

The development of the polymerase chain reaction method, which makes it possible to reproduce nucleic acids—DNA and RNA—in unlimited quantities, and the emergence of technologies for molecular selection of nucleic acids have made it possible to create artificial RNA and DNA with specified properties. Nucleic acid molecules that selectively bind certain substances are called aptamers. Based on them, drugs can be obtained that block the functions of any proteins: enzymes, receptors or regulators of gene activity. Currently, thousands of different aptamers have been obtained, which are widely used in medicine and technology.

One of the world leaders in this field is an American company Soma Logic Inc. – ​creates the so-called comomers, which are selectively selected from libraries of chemically modified nucleic acids based on the level of affinity for certain targets. Modifications at the nitrogenous base impart additional “protein-like” functionality to such aptamers, which ensures high stability of their complexes with targets. In addition, this increases the likelihood of successful selection of co-amers for those compounds for which conventional aptamers could not be selected.

The development of synthetic biology is based on a revolutionary breakthrough in the field of oligonucleotide synthesis. The synthesis of artificial genes has become possible thanks to the creation of high-performance gene synthesizers that use micro- and nanofluidic systems. Today, devices have been created that make it possible to quickly “assemble” artificial genes and/or bacterial and viral genomes, the analogues of which do not exist in nature.
An example of the development of microchip technologies is an American company LCSciences and German Febit GmbH. Biochip reactor production LCSciences using standard reagents for oligonucleotide synthesis allows you to simultaneously synthesize 4-8 thousand different oligonucleotides. Microchip reactor company Febit GmbH consists of 8 independent fragments, on each of which up to 15 thousand different oligonucleotides are simultaneously synthesized. In one day, in this way, you can obtain up to half a million oligonucleotides - the building blocks of future genes.

Among aptamers with affinity for clinically relevant targets, there are currently therapeutic drug candidates that have reached the third, key phase of clinical trials. One of them is Macugen– ​already used in clinical practice for the treatment of retinal diseases; drug for the treatment of age-related macular degeneration of the retina Fovista successfully completes the tests. And there are many similar drugs in the pipeline.

But therapy is not the only purpose of aptamers: they are of great interest to bioanalysts as recognition molecules when creating aptamer biosensors.

At IKhBFM, together with the Institute of Biophysics SB RAS (Krasnoyarsk), bioluminescent aptasensors with a switchable structure are being developed. Aptamers have been obtained that play the role of a sensor reporter block for Ca 2+ -activated photoprotein whitewash, which is a convenient bioluminescent tag. This sensor is capable of “catching” molecules of only certain proteins that need to be detected in the sample. Currently, switchable biosensors for modified blood proteins that serve as markers of diabetes are being designed using this scheme.

A new object among therapeutic nucleic acids is the messenger RNA itself. Company Moderna Therapeutics(USA) is currently conducting large-scale clinical trials of mRNA. When mRNA enters a cell, it acts as its own. As a result, the cell is able to produce proteins that can prevent or stop the development of the disease. Most of these potential therapeutic drugs are aimed against infectious diseases (influenza virus, Zika virus, cytomegalovirus, etc.) and oncological diseases.

Proteins as medicine

The enormous successes of synthetic biology in recent years have been reflected in the development of technologies for the production of therapeutic proteins, which are already widely used in the clinic. First of all, this applies to antitumor antibodies, with the help of which effective therapy for a number of oncological diseases has become possible.

Now more and more new antitumor protein drugs are appearing. An example would be a drug lactaptin, created at the ICBFM SB RAS based on a fragment of one of the main human milk proteins. Researchers have found that this peptide induces apoptosis(“suicide”) of cells from a standard tumor cell culture—human breast adenocarcinoma. Using genetic engineering methods, a number of structural analogues of lactaptin were obtained, from which the most effective was selected.

Tests on laboratory animals confirmed the safety of the drug and its antitumor and antimetastatic activity against a number of human tumors. The technology for producing lactaptin in substance and dosage form has already been developed, and the first experimental batches of the drug have been manufactured.

Therapeutic antibodies are increasingly used to treat viral infections. Specialists from the ICBFM SB RAS managed to create a humanized antibody against the tick-borne encephalitis virus using genetic engineering methods. The drug has passed all preclinical tests, proving its high effectiveness. It turned out that the protective properties of the artificial antibody are one hundred times higher than those of a commercial antibody preparation obtained from donor serum.

Invasion of heredity

Discoveries in recent years have expanded the possibilities of gene therapy, which until recently seemed like science fiction. Technologies genomic editing, based on the use of the RNA-protein system CRISPR/Cas, are able to recognize certain DNA sequences and introduce breaks in them. During "repair" ( reparations) such disorders can be corrected by mutations responsible for diseases, or new genetic elements can be introduced for therapeutic purposes.

Gene editing opens up the prospect of a radical solution to the problem of genetic diseases by modifying the genome using in vitro fertilization. The fundamental possibility of targeted changes in the genes of a human embryo has already been proven experimentally, and the creation of a technology that ensures the birth of children free from hereditary diseases is a task for the near future.

Using genomic editing, you can not only “fix” genes: this approach can be used to combat viral infections that are resistant to conventional therapy. We are talking about viruses that integrate their genome into the cellular structures of the body, where it is inaccessible to modern antiviral drugs. These viruses include HIV-1, hepatitis B viruses, papillomaviruses, polyomaviruses and a number of others. Genome editing systems can inactivate viral DNA inside a cell by cutting it into harmless fragments or introducing inactivating mutations into it.

It is obvious that the use of the CRISPR/Cas system as a means of correcting human mutations will become possible only after it is improved to ensure a high level of specificity and conduct a wide range of tests. In addition, to successfully combat dangerous viral infections, it is necessary to solve the problem of effective delivery of therapeutic agents to target cells.

First there was a stem cell

One of the fastest growing areas in medicine is cell therapy. Leading countries are already conducting clinical trials of cell technologies developed for the treatment of autoimmune, allergic, oncological and chronic viral diseases.

In Russia, pioneering work on the creation of therapeutic agents based on stem cells and cell vaccines were performed at the Institute of Fundamental and Clinical Immunology of the Siberian Branch of the Russian Academy of Sciences (Novosibirsk). As a result of research, methods for treating cancer, hepatitis B and autoimmune diseases have been developed, which have already begun to be used in the clinic on an experimental basis.

Projects for creating cell culture banks from patients with hereditary and oncological diseases for testing pharmacological drugs have become extremely relevant these days. At the Novosibirsk Scientific Center, such a project is already being implemented by an inter-institutional team under the leadership of prof. S. M. Zakiyan. Novosibirsk specialists have developed technologies for introducing mutations into cultured human cells, resulting in cell models of diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, spinal muscular atrophy, long QT syndrome and hypertrophic cardiomyopathy.

Development of methods for production from conventional somatic cells pluripotent stem, capable of turning into any cell of an adult organism, led to the emergence of cellular engineering, which makes it possible to restore damaged structures of the body. Technologies for producing three-dimensional structures for cell and tissue engineering based on biodegradable polymers are developing surprisingly quickly: vascular prostheses, three-dimensional matrices for growing cartilage tissue and constructing artificial organs.

Thus, specialists from the ICBFM SB RAS and the National Medical Research Center named after. E. N. Meshalkina (Novosibirsk) developed a technology for creating prosthetic blood vessels and heart valves using the electrospinning. Using this technology, fibers with a thickness ranging from tens of nanometers to several microns can be obtained from a polymer solution. As a result of a series of experiments, it was possible to select products with outstanding physical characteristics, which are now successfully undergoing preclinical testing. Due to their high bio- and hemocompatibility, such prostheses are eventually replaced by the body’s own tissues.

Microbiome as an object and subject of therapy

To date, the genomes of many microorganisms that infect humans have been well studied and deciphered. Research is also being conducted on complex microbiological communities that are constantly associated with humans - ​ microbiomes.

Domestic scientists have also made significant contributions to this area of ​​research. Thus, specialists from the State Research Center for Virology and Biochemistry “Vector” (Koltsovo, Novosibirsk region) were the first in the world to decipher the genomes of the Marburg and smallpox viruses, and scientists from the Institute of Chemical Biology and Microbiology of the Siberian Branch of the Russian Academy of Sciences deciphered the genomes of the tick-borne encephalitis virus, the causative agents of tick-borne borreliosis, common in the Russian Federation. Microbial communities associated with various types of ticks dangerous to humans were also studied.

In developed countries today, work is actively underway aimed at creating means of regulating the microbiome of the human body, primarily its digestive tract. As it turned out, the state of health greatly depends on the composition of the intestinal microbiome. Methods for influencing the microbiome already exist: for example, enriching it with new therapeutic bacteria, using probiotics, which favor the proliferation of beneficial bacteria, as well as the intake of bacteriophages (bacterial viruses) that selectively kill “harmful” microorganisms.

Recently, work on the creation of bacteriophage-based therapies has intensified throughout the world due to the problem of the spread of drug-resistant bacteria. Russia is one of the few countries where the use of bacteriophages in medicine is permitted. In the Russian Federation, there is an industrial production of drugs developed back in Soviet times, and in order to obtain more effective bacteriophages, it is necessary to improve them, and this problem can be solved using synthetic biology methods.

It is being solved in a number of research organizations of the Russian Federation, including the ICBFM SB RAS. The institute has characterized phage preparations industrially produced in the Russian Federation, deciphered the genomes of a number of bacteriophages, and created a collection of them, which includes unique viruses that are promising for use in medicine. The Institute’s clinic is working on mechanisms for providing personalized care to patients suffering from bacterial infections caused by drug-resistant microorganisms. The latter occur during the treatment of diabetic foot, as well as as a result of bedsores or postoperative complications. Methods for correcting disturbances in the composition of the human microbiome are also being developed.

Completely new possibilities for the use of viruses are opening up in connection with the creation of technologies for obtaining intelligent systems with highly selective action on certain cells. We are talking about oncolytic viruses, capable of infecting only tumor cells. Several such viruses are already being used experimentally in China and the United States. Work in this area is also being carried out in Russia, with the participation of specialists from Moscow and Novosibirsk research organizations: IMB RAS, SSC VB “Vector”, Novosibirsk State University and ICBFM SB RAS.

The rapid development of synthetic biology gives reason to expect in the coming years important discoveries and the emergence of new biomedical technologies that will save humanity from many problems and make it possible to actually manage health, and not just treat hereditary and “acquired” diseases.

The scope of research in this area is extremely wide. Already available gadgets are not just toys, but really useful devices that daily provide a person with the information necessary to control and maintain health. New technologies for rapid in-depth examination make it possible to predict or timely detect the development of a disease, and personalized drugs based on “smart” information biopolymers will radically solve the problems of combating infectious and genetic diseases in the very near future.

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