## 1 Introduction  
The trend in the development of modern pharmacology is the transition from the use of small molecules to the use of protein drugs. Almost a third of all pharmaceuticals in development are of a protein nature (for example, antibodies, vaccines, enzymes, hormones, cytokines, and growth factors), and their share continues to grow [1, 2]. Unlike small molecules, proteins can only be obtained in the expression system of living organisms. However, their extraction from natural hosts is often expensive, carries a risk of disease transmission, or has ethical problems. The solution is to use transgenic organisms that produce large amounts of foreign (recombinant) proteins. Moreover, the development of genetic engineering made the appearance of protein drugs possible. The recombinant protein market is projected to exceed USD 3.9 billion by 2024 [3], primarily due to therapeutic proteins. Unfortunately, these figures are due to the price of modern biopharmaceuticals, which are often inaccessible to the vast majority of the world's population. In the US, the average cost of protein drugs is 25 times higher than low molecular weight preparations. Although recombinant insulin has been on the market for five decades, its cost is still high. This is due to the high cost of equipment (fermenters) combined with the need to isolate, purify, store and transport the target substance under sterile and low-temperature conditions [4]. Most of these disadvantages can be eliminated by the production of protein preparations using transgenic plant producers. The key features of plants in comparison with other systems of protein synthesis (bacteria, yeast, cell cultures, and whole animal organisms) are infectious safety for humans (plants are not infected with human viruses and prions), extremely low cost of cultivation, as well as the possibility of oral administration preparations in the form of edible producer plants. Oral administration eliminates the most difficult and expensive procedures of isolating and purifying the target protein (accounting for up to 80% of the costs in the production of protein preparations) [5,6]. Plant cells surrounded by a cellulose cell wall can provide long-term storage of the recombinant protein and its protection from the acidic environment of the stomach [4]. However, the production of mammalian proteins in plants is associated with a number of difficulties. A feature of transgenic plants is the possible loss of the activity of the target gene, even successfully introduced into the genome and controlled with a strong promoter. The phenomenon of silencing, which means loss of expression of transferred genes in transgenic plants, was discovered in the early 1990s. The study of this phenomenon showed that the frequency of inactivation of transgenes depends on the number of their copies integrated into the plant genome, as well as the peculiarities of the organization of the insertion (the presence of duplications, vector fragments, etc.) and the site of insertion [7]. Loss of expression can occur at the transcriptional or posttranscriptional stage, in most cases with the participation of small interfering RNAs (miRNAs) [8]. This phenomenon is of great importance since, during the industrial production of a recombinant protein, it is necessary to achieve a stable level of its content in the tissues of the producer organism. Transgenic tobacco plants synthesizing bovine interferon-gamma were previously obtained in the laboratory of genetic and cellular engineering of plants, Department of Genetics and Biotechnology, St. Petersburg State University [9,10]. Tobacco was used as a model to evaluate the possibility of obtaining immunomodulatory plants for use in animal husbandry. Two lines were selected (B6 and 311), which demonstrated stable inheritance and expression of the introduced gene, as well as the presence of interferon-gamma protein in tissues. The antiviral activity of plant-made interferon was confirmed in bovine cell culture [6,11].