Effect of modification of siRNA molecules delivered with aminopropylsilanol nanoparticles on suppression of A/H5N1 virus in cell culture.

Autor: Repkova M; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS, pr. Lavrent'eva 8, Novosibirsk 630090, Russia., Mazurkov O; FBRI State Research Center of Virology and Biotechnology 'Vector' Rospotrebnadzor, Koltsovo, Novosibirsk 630559, Russia., Filippova E; FBRI State Research Center of Virology and Biotechnology 'Vector' Rospotrebnadzor, Koltsovo, Novosibirsk 630559, Russia., Protsenko M; FBRI State Research Center of Virology and Biotechnology 'Vector' Rospotrebnadzor, Koltsovo, Novosibirsk 630559, Russia., Mazurkova N; FBRI State Research Center of Virology and Biotechnology 'Vector' Rospotrebnadzor, Koltsovo, Novosibirsk 630559, Russia., Meschaninova M; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS, pr. Lavrent'eva 8, Novosibirsk 630090, Russia., Levina A; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS, pr. Lavrent'eva 8, Novosibirsk 630090, Russia., Zarytova V; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS, pr. Lavrent'eva 8, Novosibirsk 630090, Russia. Electronic address: zarytova@niboch.nsc.ru.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2024 Dec; Vol. 1868 (12), pp. 130727. Date of Electronic Publication: 2024 Oct 20.
DOI: 10.1016/j.bbagen.2024.130727
Abstrakt: The application of siRNAs as antiviral agents is limited by several obstacles including their poor penetration into cells and instability in biological media. To overcome these problems, we used non-agglomerated aminopropylsilanol nanoparticles (NP) to deliver siRNA into cells. All studied siRNAs had identical nucleoside sequences comprising phosphodiester or phosphorothioate (PS) internucleotide groups and the 2'-OMe and/or 2'-F groups in nucleoside units at different positions of RNA. The siRNA molecules were attached to NP, thus forming the NP-siRNA nanocomplexes. We studied the effect of siRNA modification in the nanocomplexes on suppressing the highly pathogenic influenza A/H5N1 virus replication. The results demonstrated that all siRNA-containing nanocomplexes inhibited the replication of the A/H5N1 virus by 1-3 orders of magnitude. The nanocomplexes containing partially modified siRNAs exhibited the most pronounced inhibition with an efficacy of 900-fold. This result was achieved by using siRNA consisting of the canonical 19-bp RNA duplex with the 3'-dTdT dangling ends, with the antisense strand in this duplex being protected from endonucleases (one U Me A site within the strand). The additional modifications of siRNA reduce their antiviral activity. Promising sense strands for loading into the RISC complex are likely to be phosphodiester sequences that contain dTdT at the 3' end (such as S 4 ) to be protected against exonucleases. The sense strands of this type can probably be the most suitable for designing siRNAs as therapeutic agents. The proposed NP-siRNA nanocomplexes that consisted of low toxic and non-agglomerated aminopropylsilanol nanoparticles and siRNA molecules could be hopeful agents for gene silencing.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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