Abstract
Anti-influenza drugs and vaccines have a limited effect due to the high mutation rate of virus genome. The direct impact on the conservative virus genome regions should significantly improve therapeutic effectiveness. The RNA interference mechanism (RNAi) is one of the modern approaches used to solve this problem. In this work, we have investigated the antiviral activity of small interfering RNA (siRNA) against the influenza A/PR/8/34 (H1N1), targeting conserved regions of NP and PA. Polycations were used for intracellular siRNA delivery: chitosan's derivatives (methylglycol and quaternized chitosan), polyethyleneimine, lipofectamine, and hybrid organic/non-organic microcapsules. A comparative study of these delivery systems with fluorescent labeled siRNA was conducted. The antiviral activity of three small interfering RNAs targeting the NP (NP-717, NP-1496) and PA (PA-1630) influenza A viruses genes was demonstrated, depending on the chosen carrier. The most effective intracellular delivery and antiviral activity were observed for hybrid microcapsules.
Highlights
Механизм РНК-интерференции открывает широкие возможности при создании новых препаратов для лечения гриппа
We have investigated the antiviral activity of small interfering RNA against the influenza A/PR/8/34 (H1N1), targeting conserved regions of NP and PA
The most effective intracellular delivery and antiviral activity were observed for hybrid microcapsules
Summary
Механизм РНК-интерференции открывает широкие возможности при создании новых препаратов для лечения гриппа. Проведена сравнительная оценка различных носителей для внутриклеточной доставки малых интерферирующих РНК: метилгликольхитозана, кватернизованного хитозана, полиэтиленимина и гибридных микрокапсул на основе полиаргинина с неорганическими компонентами. Сравнение эффективностей ингибирования вируса гриппа А in vitro комплексами малых интерферирующих РНК с производными хитозана, полиэтиленимином и гибридными микрокапсулами на основе полиаргинина с неорганическими компонентами. Petrova-Brodskaya А.V.1,2, Bondarenko А.B.1,3, Timin А.S.2,4, Plotnikova М.А.1, Afanas’ev М.V.1,3, Semenova А.А.5, Lebedev K.I.1, Gorshkov А.N.1,7, Gorshkova М.Yu., Egorov V.V.1, Klotchenko S.А.1, Vasin А.V.1,2. COMPARISON OF INFLUENZA A VIRUS INHIBITION IN VITRO BY siRNA COMPLEXES WITH CHITOSAN DERIVATIVES, POLYETHYLENEIMINE AND HYBRID POLYARGININE-INORGANIC. For citation: Petrova-Brodskaya А.V., Bondarenko А.B., Timin А.S., Plotnikova М.А., Afanas’ev М.V., Semenova А.А., Lebedev K.I., Gorshkov А.N., Gorshkova М.Yu., Egorov V.V., Klotchenko S.А., Vasin А.V. Comparison of influenza A virus inhibition in vitro by siRNA complexes with chitosan derivatives, polyethyleneimine and hybrid polyarginine-inorganic microcapsules. Information about authors: Petrova-Brodskaya А.V., http://orcid.org/0000-0001-5130-3755; Timin А.S., http://orcid.org/0000-0002-0276-7892; Plotnikova М.A., https://orcid.org/0000-0001-8196-3156; Gorshkov А.N., http://orcid.org/0000-0003-2303-1144; Gorshkova М.Yu., http://orcid.org/0000-0002-6249-1031; Egorov V.V., http://orcid.org/0000-0002-3670-8962; Klotchenko S.A., http://orcid.org/0000-0003-0289-6560; Vasin А.V., http://orcid.org/0000-0002-1391-7139
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