Inhibition of influenza A virus by mixed siRNAs, targeting the PA, NP, and NS genes, delivered by hybrid microcarriers; Antiviral Research; Vol. 158

Detalles Bibliográficos
Parent link:Antiviral Research
Vol. 158.— 2018.— [P. 147-160]
Autor Corporativo: Национальный исследовательский Томский политехнический университет Исследовательская школа химических и биомедицинских технологий (ИШХБМТ)
Outros autores: Brodskaya A. V. Aleksandra Vladimirovna, Timin A. S. Aleksandr Sergeevich, Gorshkov A. N. Andrey Nikolaevich, Muslimov A. N. Andrey Nikolaevich, Bondarenko A. B. Andrey Borisovich, Tarakanchikova Ya. V. Yana Vladimirovna, Zabrodskaya Ya. A. Yana Alekseevna, Iljinskaya E. V., Sakhenberg E. I. Elena Igorevna, Sukhorukov G. B. Gleb Borisovich, Vasin A. V.
Summary:Title screen
In the present study, a highly effective carrier system has been developed for the delivery of antiviral siRNA mixtures. The developed hybrid microcarriers, made of biodegradable polymers and SiO2 nanostructures, more efficiently mediate cellular uptake of siRNA than commercially available liposome-based reagents and polyethyleneimine (PEI); they also demonstrate low in vitro toxicity and protection of siRNA from RNase degradation. A series of siRNA designs (targeting the most conserved regions of three influenza A virus (IAV) genes: NP, NS, and PA) were screened in vitro using RT-qPCR, ELISA analysis, and hemagglutination assay. Based on the results of screening, the three most effective siRNAs (PA-1630, NP-717, and NS-777) were selected for in situ encapsulation into hybrid microcarriers. It was revealed that pre-treatment of cells with a mixture of PA-1630, NP-717, and NS-777 siRNAs, delivered by hybrid microcarriers, provided stronger inhibition of viral M1 mRNA expression and control of NP protein level, after viral infection, than single pre-treatment by any of three encapsulated siRNAs used in the study. Moreover, the effective inhibition of replication in several IAV subtypes (H1N1, H1N1pdm, H5N2, and H7N9) using a cocktail of the three selected siRNAs, delivered by our hybrid capsules to the cells, was achieved. In conclusion, we have developed a proof-of-principle which shows that our hybrid microcarrier technology (utilizing a therapeutic siRNA cocktail) may represent a promising approach in anti-influenza therapy.
Режим доступа: по договору с организацией-держателем ресурса
Idioma:inglés
Publicado: 2018
Subjects:
Acceso en liña:https://doi.org/10.1016/j.antiviral.2018.08.003
Formato: Electrónico Capítulo de libro
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=660145

MARC

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200 1 |a Inhibition of influenza A virus by mixed siRNAs, targeting the PA, NP, and NS genes, delivered by hybrid microcarriers  |f A. V. Brodskaya [et al.] 
203 |a Text  |c electronic 
300 |a Title screen 
320 |a [References: 51 tit.] 
330 |a In the present study, a highly effective carrier system has been developed for the delivery of antiviral siRNA mixtures. The developed hybrid microcarriers, made of biodegradable polymers and SiO2 nanostructures, more efficiently mediate cellular uptake of siRNA than commercially available liposome-based reagents and polyethyleneimine (PEI); they also demonstrate low in vitro toxicity and protection of siRNA from RNase degradation. A series of siRNA designs (targeting the most conserved regions of three influenza A virus (IAV) genes: NP, NS, and PA) were screened in vitro using RT-qPCR, ELISA analysis, and hemagglutination assay. Based on the results of screening, the three most effective siRNAs (PA-1630, NP-717, and NS-777) were selected for in situ encapsulation into hybrid microcarriers. It was revealed that pre-treatment of cells with a mixture of PA-1630, NP-717, and NS-777 siRNAs, delivered by hybrid microcarriers, provided stronger inhibition of viral M1 mRNA expression and control of NP protein level, after viral infection, than single pre-treatment by any of three encapsulated siRNAs used in the study. Moreover, the effective inhibition of replication in several IAV subtypes (H1N1, H1N1pdm, H5N2, and H7N9) using a cocktail of the three selected siRNAs, delivered by our hybrid capsules to the cells, was achieved. In conclusion, we have developed a proof-of-principle which shows that our hybrid microcarrier technology (utilizing a therapeutic siRNA cocktail) may represent a promising approach in anti-influenza therapy. 
333 |a Режим доступа: по договору с организацией-держателем ресурса 
461 |t Antiviral Research 
463 |t Vol. 158  |v [P. 147-160]  |d 2018 
610 1 |a электронный ресурс 
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610 1 |a siRNA delivery 
610 1 |a RNAi therapy 
610 1 |a influenza A virus 
610 1 |a hybrid microcontainers 
610 1 |a вирусы 
610 1 |a грипп 
610 1 |a терапия 
701 1 |a Brodskaya  |b A. V.  |g Aleksandra Vladimirovna 
701 1 |a Timin  |b A. S.  |c Chemist  |c Associate Scientist of Tomsk Polytechnic University  |f 1989-  |g Aleksandr Sergeevich  |3 (RuTPU)RU\TPU\pers\37036 
701 1 |a Gorshkov  |b A. N.  |g Andrey Nikolaevich 
701 1 |a Muslimov  |b A. N.  |g Andrey Nikolaevich 
701 1 |a Bondarenko  |b A. B.  |g Andrey Borisovich 
701 1 |a Tarakanchikova  |b Ya. V.  |g Yana Vladimirovna 
701 1 |a Zabrodskaya  |b Ya. A.  |g Yana Alekseevna 
701 1 |a Iljinskaya  |b E. V. 
701 1 |a Sakhenberg  |b E. I.  |g Elena Igorevna 
701 1 |a Sukhorukov  |b G. B.  |g Gleb Borisovich 
701 1 |a Vasin  |b A. V. 
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