Аддитивный эффект синтетических малых интерферирующих РНК в отношении респираторно-синцитиального вируса 1 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства, 115522, г.Москва, Российская Федерация 2 Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М.Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет), 119991, г.Москва, Российская Федерация 3 Федеральное государственное бюджетное научное учреждение «Научно-исследовательский институт вакцин и сывороток им.И.И

МИР 19 ® -первый в мире специфический противовирусный препарат для лечения COVID-19: разработка и доклинические исследования 1 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства, 115522, г.Москва, Российская Федерация 2 Федеральное государственное автономное образовательное учр еждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И.Пирогова» Министерства здравоохранения Российской Федерации, 117997, г.Москва, Российская Федерация 3 Федеральное государственное бюджетное научное учреждение «Научно-исследовательский институт вакцин и сывороток им.И.И

Результаты I и II фазы клинических исследований препарата МИР 19 ® 1 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства, 115522, г.Москва, Российская Федерация 2 Федеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И.Пирогова» Министерства здравоохранения Российской Федерации, 117997, г.Москва, Российская Федерация 3 Федеральное государственное бюджетное научное учреждение «Научно-исследовательский институт вакцин и сывороток им.И.И.Мечникова» Министерства науки и высшего образования Российской Федерации, 105064, г.Москва, Российская Федерация 4 Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М

Bronchial asthma (BA) is one of the most common chronic inflammatory disease of airways. There are huge experimental data indicating that Th2-cytokines IL-4 and IL-13 play a key role in BA pathogenesis. They are implicated in the IgE synthesis, eosinophil infiltration to the lungs and in the development of airway hyperreactivity (AHR), that makes these cytokines the promising targets. Neutralization of IL-4 and IL-13 or its common receptor chain (IL-4Rα) by monoclonal antibodies substantially reduce asthma symptoms. RNA interference provides a novel method for regulation of gene expression by siRNA molecules. In this study we evaluated whether the siRNA targeted to IL-4 and IL-13 reduce BA symptoms in mice model. Experimental BA was induced in BALB/c mice by sensitization to ovalbumin allergen followed by intranasal challenge. The intranasal delivery of siRNAs targeted to IL-4 and IL-13 inhibited the lung expression of these cytokines by more than 50% that led to the attenuation of AHR and pulmonary inflammation; the quantity of eosinophils in lungs which are one of the major inflammatory cells involved in allergic asthma pathogenesis decreased by more than 50% after siRNA treatment. These data support the possibility of a dual IL-4 and IL-13 inhibition by locally delivered siRNAs which in turn leads to the suppression of allergen-induced pulmonary inflammation and AHR.

Влияние локального подавления экспрессии гена Stat3 на нейтрофильное воспаление легких в экспериментальной модели на мышах1 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства, 115522, г.Москва, Российская Федерация 2 Федеральное государственное бюджетное образовательное учреждение высшего образования Московская государственная академия ветеринарной медицины и биотехнологии -МВА имени К.И.Скрябина Министер-

This article is a continuation of the series of works devoted to determining the frequency of mutations associated with the development of common monogenic diseases among the representatives of the Russian population. The frequencies of mutations in the genes HFE , ATP7B , and MEFV in primary blood donors who identify themselves as Russians and permanently reside in the Russian Federation were established. The method of adjacent probes was used for SNP genotyping. Genotyping revealed 57 carriers of the C282Y mutation of the HFE gene, the most significant in the development of hemochromatosis type I (the frequency in the sample of 911 donors was 6.3%, or 1 : 16), and 18 carriers of the H1069Q mutation in the ATP7B gene, associated with the development of Wilson–Konovalov disease (the frequency in the sample of 1032 donors was 1.7%, or 1 : 57). A high frequency of the K695R mutation in the MEFV gene (the frequency in the sample of 1212 donors was 7.3%, or 1 : 14), associated with the development of familial Mediterranean fever, characterized by a mild phenotype and incomplete penetrance, was also established.

Background: Mouse models of allergic asthma play a crucial role in exploring of asthma pathogenesis and testing of novel anti-inflammatory drugs. Widely used acute asthma models usually developed with adjuvant (aluminum hydroxide (alum)) do not reproduce one of the main asthma feature - airway remodeling while chronic asthma model mimic the pathophysiology of human disease. Moreover, the use of alum causes distress in experimental animals and impedes the test of adjuvant-containing drugs. In this study, we aimed to develop a chronic adjuvant-free asthma model with pronounced asthmatic phenotype. Methods: Female BALB/c mice were divided into 3 groups. The first group was sensitized with intraperitoneal injections of ovalbumin (OVA) emulsified in aluminum hydroxide on days 0, 14, 28 followed by two stages of intranasally challenge with OVA on days 41-43 and 62-64. The second group was subcutaneously sensitized with the same dose of OVA without adjuvant and challenged on the same days. The third group (negative control) included mice which did not received any kind of treatment (i.e. sensitization and challenge). Serum levels of OVA-specific IgE, IgG2a and IgG1 antibodies were detected by ELISA. Airway hyper-responsiveness was measured by non-invasive plethysmography on days 44 and 65. Bronchoalveolar lavage fluids (BALF) sampled in all groups on days 45 and 66 were analyzed by light microscopy. The left lung was removed for histological analysis. The IL-4 and IFN gamma mRNA expression in BALF cells was evaluated by RT-PCR. Results: The OVA-specific IgE antibody response was two-fold increased in mice from adjuvant-free group compared to the adjuvant group that reflects reorientation of immune response towards Th2 phenotype. At the same time, the level of OVA-specific IgG1 and IgG2a antibodies was increased in the adjuvant group. Airway hyperresponsiveness to methacholine in mice of both experimental groups was two-fold higher than in control. Analysis of cell composition in BAL has shown a significant increase in eosinophil count in both experimental groups that indicate the development of allergic inflammation. Lung histology revealed airway remodeling in both experimental groups including goblet cell hyperplasia/metaplasia, thickening of airway walls, collagen deposition in the wall of distal airways. Additionally, the tendency to develop hypertrophy of bronchial smooth muscle layer was observed. Study of gene expression in BAL cells revealed the increase of IL-4 level in both adjuvant and adjuvant-free groups while IFN gamma expression in both experimental groups was similar to control group. Conclusion: We have developed a chronic adjuvant-free mouse asthma model which possesses all necessary features of the disease including airway remodeling and is more suitable for pre-clinical evaluation of novel therapeutic approaches including adjuvant-containing drugs.

The study aimed to establish the frequency of common CFTR and PAH mutations in the Russian population in first time blood donors. Genotyping of 1000 first time blood donors who identify themselves as Russians and live permanently in the Russian Federation, detected 29 carriers of CFTR mutations associated with cystic fibrosis development (carrier frequency in the sample of subjects was 2.9 %, or 1:34) and 32 carriers of PAH mutations associated with phenylketonuria development (carrier frequency in the sample of subjects was 3.2 %, or 1:31). Altogether 61 carrier of CFTR and PAH mutations was found (carrier frequency in the sample of subjects was 6.1%, or 1:16). The obtained data can be used for developing effective diagnostic guidelines for the above mentioned hereditary diseases.

A highly sensitive test system, based on the immuno-PCR method, was developed for the detection of two staphylococcal toxins: enterotoxin A (SEA) and toxic shock syndrome toxin (TSST). A key element of the developed systems was to obtain supramolecular complexes of bisbiotinylated oligodeoxynucleotides and streptavidin, which were to be used as DNA-tags. Specificity studies showed no cross-reactivity when determining SEA and TSST. The sensitivity of detection of these toxins in the culture supernatants S. aureus was not lower than 10 pg/mL.

Aqueous solutions of the fullerene C 60 (nC 60 ) were prepared by simple mixing of the solution of C 60 in N-methylpyrrolidone (MP) with deionized water or an aqueous solution of a low-molecular-weight natural substance (L-amino acids, monosaccharides, peptides, or glycerol) used as stabilizing agents (SAs) followed by exhaustive dialysis against distilled water. During dialysis, all low-molecular-weight compounds are removed through the pores and the fullerene clusters remain in the solution. The efficiency of conversion of C 60 from the crystalline state to the solution approaches the quantitative value, and solutions with a C 60 concentration of up to 250 mg/L can be obtained; moreover, these solutions are stable for at least 10–12 months. The formation of insoluble aggregates has been observed when basic and acidic organic compounds were used as SA. The UV-VIS spectra of solutions have a profile characteristic of nC 60 solutions obtained by other well-known procedures (maxima at 220, 265, 340, and 450 nm). Mass spectra of aqueous solutions and FTIR spectra of dried nC60 samples were indicative of the possible partial hydroxylation of the fullerene. A measurement of the sizes and ξ potential of the C 60 particles in solutions by the dynamic light scattering method showed that their average diameter is about 100 nm and the charge is −30 mV, whereas the electron microscopy data demonstrated that the particles have a typical size of approximately 20 nm and contain both crystalline and amorphous phases. The proposed method is promising for the preparation of solutions of endofullerenes and, probably, higher fullerenes.