Abstract
RNA-mediated gene silencing or RNA silencing is a gene regulation mechanism in eukaryotes involved in RNA-mediated sequence-specific RNA degradation in the cytoplasm followed by chromatin remodelling in the nucleus that plays a crucial role in differentiation and developmental processes. Besides, the RNA silencing machinery serves as an innate defense response against viruses and transposons and is responsible for down regulating transgene expression. Therefore, the induction of RNA silencing in producer cells limits the production of recombinant proteins and of (recombinant) virus particles for use as vaccines or in gene therapies.
Viruses counteract the RNA silencing response by expressing RNA silencing suppressors (RSSs) in infected cells, thereby allowing the virus to reach higher titers.
We employed viral RSSs for improving the productivity of eukaryotic production systems. We here describe the application of viral RSSs in enhancing the production of pharmaceutical proteins including monoclonal antibodies and virus particles in mammalian cell lines.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Butler, M. (2005) Animal cell cultures: recent achievements and perspectives in the production of biopharmaceuticals. Appl. Microbiol Biotechnol. 68(3):283–291.
Haasnoot, J., de Vries, W., Geutjes, E.J., Prins, M., de Haan, P., and Berkhout, B. (2007) The ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathogens 3, e86
Hammond, S.M., Bernstein, E., Beach, D., and Hannon, G.J. (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404, 293–296.
Kasschau, K.D. and Carrington, J.C. (1998) A counter defensive strategy of plant viruses: suppression of posttranscriptional gene silencing. Cell 95, 461–470.
Li, H., Li, W.X., and Ding, S.W. (2002) Induction and suppression of RNA silencing by an animal virus. Science 296, 1319–1321.
Mattick, J.S. (2007) A new paradigm for developmental biology. J. Exp. Biol. 210, 1526–1547.
Schramke, V. and Allshire, R. (2003) Hairpin RNAs and retrotransposon LTRs affect RNAi and chromatin-based gene silencing. Science 301, 1069–1074
Wang, X.H., Aliyari, R., Li, W.X., Li, H.W., Kim, K., Carthew, R., Atkinson, P., and Ding, S.W. (2006) RNA interference directs innate immunity against viruses in adult Drosophila. Science 312, 452–454.
Wilkins, C., Dishongh, R., Moore, S.C., Whitt, M.A., Chow, M., and Machaca, K. (2005) RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436, 1044–1047.
Wurm, F.M. (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nature Biotech. 22, 1393–1398.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media B.V.
About this paper
Cite this paper
de Haan, P., Engel, A., de Vries, W., van der Velden, J., van Holst, GJ., Arnoldussen, E. (2010). RNA Silencing Suppressors Boost the Production of Recombinant Proteins and Viruses. In: Noll, T. (eds) Cells and Culture. ESACT Proceedings, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3419-9_2
Download citation
DOI: https://doi.org/10.1007/978-90-481-3419-9_2
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-3418-2
Online ISBN: 978-90-481-3419-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)