Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles
Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the intracel...
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| Format: | Article |
| Language: | Russian |
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Central Research Institute for Epidemiology
2024-12-01
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| Series: | Журнал микробиологии, эпидемиологии и иммунобиологии |
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| Online Access: | https://microbiol.crie.ru/jour/article/viewFile/18626/1553 |
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| author | Marina N. Repkova Asya S. Levina Oleg Yu. Mazurkov Elena V. Makarevich Ekaterina I. Filippova Natalya A. Mazurkova Valentina F. Zarytova |
| author_facet | Marina N. Repkova Asya S. Levina Oleg Yu. Mazurkov Elena V. Makarevich Ekaterina I. Filippova Natalya A. Mazurkova Valentina F. Zarytova |
| author_sort | Marina N. Repkova |
| collection | DOAJ |
| description | Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the intracellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task.
The aim of the study is to create nanocomplexes consisting of aminopropylsilanol nanoparticles and short interfering RNA (siRNA) to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in vitro.
Materials and methods. MDCK cells, influenza virus A/chicken/Kurgan/05/2005 (A/H5N1), aminopropylsilanol nanoparticles, and native and modified siRNA molecules.
Results and discussion. We have prepared unique Si~NH2/siRNA nanocomplexes, which consist of aminopropylsilanol nanoparticles and siRNA molecules, which enable cell penetration and selective interaction with target nucleic acids, respectively. The antiviral activity of the proposed nanocomplexes has been studied on MDCK cells infected with the influenza A/H5N1 virus. It has been shown that the double-stranded siRNA molecules in the nanocomplexes, which act by the RNA interference mechanism, are more efficient in inhibiting the replication of the influenza virus than the corresponding single-stranded RNA fragments. The most effective nanocomplex that contained siRNA targeted at the chosen region of mRNA segment 5 of the viral genome reduced virus replication in the culture by a factor of 630. We have shown that non-agglomerated and water-soluble aminopropylsilanol nanoparticles are low-toxic, capable of delivering siRNA into cells and protecting siRNA in the Si~NH2/siRNA nanocomplexes from hydrolysis by cellular nucleases.
Conclusion. The biological activity of the created nanocomplexes has been demonstrated by the example of highly effective selective suppression of influenza A/chicken/Kurgan/05/2005 virus replication in the cellular system. |
| format | Article |
| id | doaj-art-b63bee6c14874df5bb60fe1bbc12851f |
| institution | Kabale University |
| issn | 0372-9311 2686-7613 |
| language | Russian |
| publishDate | 2024-12-01 |
| publisher | Central Research Institute for Epidemiology |
| record_format | Article |
| series | Журнал микробиологии, эпидемиологии и иммунобиологии |
| spelling | doaj-art-b63bee6c14874df5bb60fe1bbc12851f2025-02-06T21:11:31ZrusCentral Research Institute for EpidemiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-76132024-12-01101679480210.36233/0372-9311-5752800Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticlesMarina N. Repkova0https://orcid.org/0000-0002-7108-9036Asya S. Levina1https://orcid.org/0000-0003-2423-3805Oleg Yu. Mazurkov2https://orcid.org/0000-0001-8164-4091Elena V. Makarevich3https://orcid.org/0000-0002-5146-8979Ekaterina I. Filippova4https://orcid.org/0000-0001-9554-4462Natalya A. Mazurkova5https://orcid.org/0000-0002-1896-2684Valentina F. Zarytova6https://orcid.org/0000-0002-9579-9972Institute of Chemical Biology and Fundamental MedicineInstitute of Chemical Biology and Fundamental MedicineState Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”Institute of Chemical Biology and Fundamental MedicineRelevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the intracellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task. The aim of the study is to create nanocomplexes consisting of aminopropylsilanol nanoparticles and short interfering RNA (siRNA) to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in vitro. Materials and methods. MDCK cells, influenza virus A/chicken/Kurgan/05/2005 (A/H5N1), aminopropylsilanol nanoparticles, and native and modified siRNA molecules. Results and discussion. We have prepared unique Si~NH2/siRNA nanocomplexes, which consist of aminopropylsilanol nanoparticles and siRNA molecules, which enable cell penetration and selective interaction with target nucleic acids, respectively. The antiviral activity of the proposed nanocomplexes has been studied on MDCK cells infected with the influenza A/H5N1 virus. It has been shown that the double-stranded siRNA molecules in the nanocomplexes, which act by the RNA interference mechanism, are more efficient in inhibiting the replication of the influenza virus than the corresponding single-stranded RNA fragments. The most effective nanocomplex that contained siRNA targeted at the chosen region of mRNA segment 5 of the viral genome reduced virus replication in the culture by a factor of 630. We have shown that non-agglomerated and water-soluble aminopropylsilanol nanoparticles are low-toxic, capable of delivering siRNA into cells and protecting siRNA in the Si~NH2/siRNA nanocomplexes from hydrolysis by cellular nucleases. Conclusion. The biological activity of the created nanocomplexes has been demonstrated by the example of highly effective selective suppression of influenza A/chicken/Kurgan/05/2005 virus replication in the cellular system.https://microbiol.crie.ru/jour/article/viewFile/18626/1553aminopropylsilanol nanoparticlesnanocomplexessirnaantiviral activityinfluenza a/h5n1 virus |
| spellingShingle | Marina N. Repkova Asya S. Levina Oleg Yu. Mazurkov Elena V. Makarevich Ekaterina I. Filippova Natalya A. Mazurkova Valentina F. Zarytova Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles Журнал микробиологии, эпидемиологии и иммунобиологии aminopropylsilanol nanoparticles nanocomplexes sirna antiviral activity influenza a/h5n1 virus |
| title | Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles |
| title_full | Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles |
| title_fullStr | Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles |
| title_full_unstemmed | Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles |
| title_short | Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles |
| title_sort | selective suppression of influenza a h5n1 virus replication i in vitro i using nanocomplexes consisting of sirna and aminopropylsilanol nanoparticles |
| topic | aminopropylsilanol nanoparticles nanocomplexes sirna antiviral activity influenza a/h5n1 virus |
| url | https://microbiol.crie.ru/jour/article/viewFile/18626/1553 |
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