Abstract
Human adenoviruses, in particular D8, D19, and D37, cause ocular infections. Currently, there is no available causally directed treatment, which efficiently counteracts adenoviral infectious diseases. In our previous work, we showed that gene silencing by means of RNA interference is an effective approach for downregulation of human species D adenoviruses replication. In this study, we compared the biological activity of siRNAs and their modified analogs targeting human species D adenoviruses DNA polymerase. We found that one of selectively 2’-O-methyl modified siRNAs mediates stable and long-lasting suppression of the target gene (12 days post transfection). We suppose that this siRNA can be used as a potential therapeutic agent against human species D adenoviruses.
References
Lynch J.P., 3rd, Fishbein M., Echavarria M. 2011. Adenovirus. Semin. Respir. Crit. Care Med. 32, 494–511.
Myers G.D., Krance R.A., Weiss H., Kuehnle I., Demmler G., Heslop H.E., Bollard C.M. 2005. Adenovirus infection rates in pediatric recipients of alternate donor allogeneic bone marrow transplants receiving either antithymocyte globulin (ATG) or alemtuzumab (Campath). Bone Marrow Transplant. 36, 1001–1008.
Trovato G.M., Martines G.F., Pirri C., Trovato F.M., Castro A., Garozzo A., Catalano D. 2012. Obesityindependent association of human adenovirus Ad37 seropositivity with nonalcoholic fatty liver disease. J. Clin. Gastroenterol. 46, e46–e54.
Gonzalez-Lopez J.J., Morcillo-Laiz R., Munoz-Negrete F.J. 2013. Adenoviral keratoconjunctivitis: An update. Arch. Soc. Esp. Oftalmol. 88, 108–115.
Alexeev V.N., Martynova E.B., Zhukova E.A. 2005. Pathogenically based treatment of adenoviral eye diseases. Clin. Ophtalmol. Russ. Med. J. 4, 146–149.
Kneidinger D., Ibrisimovic M., Lion T., Klein R. 2012. Inhibition of adenovirus multiplication by short interfering RNAs directly or indirectly targeting the viral DNA replication machinery. Antiviral Res. 94, 195–207.
Nikitenko N.A., Speiseder T., Groitl P., Spirin P.V., Prokofjeva M.M., Lebedev T.D., Rubtsov P.M., Lam E., Riecken K., Fehse B., Dobner T., Prassolov V.S. 2015. Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis. Biochimie. 113, 10–16.
Elbashir S.M., Harborth J., Lendeckel W., Yalcin A., Weber K., Tuschl T. 2001. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 411, 494–498.
Spirin P.V., Baskaran D., Orlova N.N., Rulina A.V., Nikitenko N.A., Chernolovskaya E.L., Zenkova M.A., Vlassov V.V., Rubtsov P.M., Chumakov P.M., Stocking C., Prassolov V.S. 2010. Downregulation of activated leukemic oncogenes AML1-ETO and RUNX1(K83N) expression with RNA-interference. Mol. Biol. (Moscow). 44 (5), 776–786.
Spirin P.V., Lebedev T.D., Orlova N.N., Gornostaeva A.S., Prokofjeva M.M., Nikitenko N.A., Dmitriev S.E., Buzdin A.A., Borisov N.M., Aliper A.M., Garazha A.V., Rubtsov P.M., Stocking C., Prassolov V.S. 2014. Silencing AML1-ETO gene expression leads to simultaneous activation of both pro-apoptotic and proliferation signaling. Leukemia. 28, 2222–2228.
Spirin P.V., Nikitenko N.A., Lebedev T.D., Rubtsov P.M., Stocking C., Prasolov V.S. 2011. Modulation of activated oncogene c-kit expression with RNA-interference. Mol. Biol. (Moscow). 45 (6), 950–958.
Chu C.Y., Rana T.M. 2008. Potent RNAi by short RNA triggers. RNA. 14, 1714–1719.
Chernolovskaya E.L., Zenkova M.A. 2010. Chemical modification of siRNA. Curr. Opin. Mol. Ther. 12, 158–167.
Volkov A.A., Kruglova N.S., Meschaninova M.I., Venyaminova A.G., Zenkova M.A., Vlassov V.V., Chernolovskaya E.L. 2009. Selective protection of nucleasesensitive sites in siRNA prolongs silencing effect. Oligonucleotides. 19, 191–202.
Nikitenko N.A., Prasolov V.S. 2013. Nonviral methods of delivery and therapeutic applications of small interfering RNAs. Acta Naturae. 5, 36–56.
Petrova-Kruglova N.S., Meschaninova M.I., Venyaminova A.G., Zenkova M.A., Vlassov V.V., Chernolovskaya E.L. 2010. 2’-O-methyl-modified anti- MDR1 fork-siRNA duplexes exhibiting high nuclease resistance and prolonged silencing activity. Oligonucleotides. 20, 297–308.
Khvorova A., Reynolds A., Jayasena S.D. 2003. Functional siRNAs and miRNAs exhibit strand bias. Cell. 115, 209–216.
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Original Russian Text © N.A. Nikitenko, T. Speiseder, E.L. Chernolovskaya, M.A. Zenkova, T. Dobner, V.S. Prassolov, 2016, published in Molekulyarnaya Biologiya, 2016, Vol. 50, No. 1, pp. 188–192.
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Nikitenko, N.A., Speiseder, T., Chernolovskaya, E.L. et al. Downregulation of human adenovirus DNA polymerase gene by modified siRNAs. Mol Biol 50, 164–167 (2016). https://doi.org/10.1134/S0026893316010155
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DOI: https://doi.org/10.1134/S0026893316010155