Skip to main content
Log in

Downregulation of human adenovirus DNA polymerase gene by modified siRNAs

  • Short Communications
  • Published:
Molecular Biology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Lynch J.P., 3rd, Fishbein M., Echavarria M. 2011. Adenovirus. Semin. Respir. Crit. Care Med. 32, 494–511.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. Gonzalez-Lopez J.J., Morcillo-Laiz R., Munoz-Negrete F.J. 2013. Adenoviral keratoconjunctivitis: An update. Arch. Soc. Esp. Oftalmol. 88, 108–115.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Google Scholar 

  6. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. Chu C.Y., Rana T.M. 2008. Potent RNAi by short RNA triggers. RNA. 14, 1714–1719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chernolovskaya E.L., Zenkova M.A. 2010. Chemical modification of siRNA. Curr. Opin. Mol. Ther. 12, 158–167.

    CAS  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. Nikitenko N.A., Prasolov V.S. 2013. Nonviral methods of delivery and therapeutic applications of small interfering RNAs. Acta Naturae. 5, 36–56.

    Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. Khvorova A., Reynolds A., Jayasena S.D. 2003. Functional siRNAs and miRNAs exhibit strand bias. Cell. 115, 209–216.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. S. Prassolov.

Additional information

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893316010155

Keywords

Navigation