© 2008 Oxford University Press
This article appears in the following Nucleic Acid Symposium Series issue: Joint Symposium of the 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids and the 35th International Symposium on Nucleic Acids Chemistry [View the issue table of contents]
Inhibition of picornaviruses by means of RNA interference
1Institute of Industrial Genetics, University of Stuttgart, Stuttgart, Germany; 2Institute of Chemistry and Biochemistry, Free University Berlin, Berlin, Thielallee 63, 14195 Berlin, Germany; 3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland; 4Department of Virology, Institute for Infectious Diseases, Charité - University Medicine Berlin, Berlin, Germany; 5Department of Cardiology and Pneumology, Charité - University Medicine Berlin, Berlin, Germany;
*Corresponding Author. E-mail: jens.kurreck{at}iig.unistuttgart.de
Abstract
Picornaviruses are a class of RNA viruses with a single-stranded genome in positive orientation. Since the prospects of treatment are limited, we employ RNA interference (RNAi) as an antiviral tool to inhibit different picornaviruses. We identified small interfering RNAs (siRNAs) against the 3D RNA dependent RNA polymerase of coxsackievirus B3 that were capable of efficiently inhibiting the virus. Targeting of the conserved 5' UTR of the virus turned out to be a challenging task since stable structures of this region are detrimental to silencing. We developed a rational strategy to solve this problem and found an siRNA containing locked nucleic acids (LNAs) to possess high antiviral potency. To analyse the mechanism of virus inhibition in more detail, LNAs were incorporated into the siRNA to inactivate either of the siRNA strands. These experiments clearly revealed that only the genomic plus-strand but not the intermediary synthesised minus-strand can be targeted by siRNAs. Furthermore, siRNAs were employed to silence the virus receptor on the host cell and thus prevent viral spread.
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