Application of small interfering RNAs modified by unlocked nucleic acid (UNA) to inhibit the heart-pathogenic coxsackievirus B3

This study describes the first application of unlocked nucleic acid (UNA)-modified small interfering RNAs (siRNAs) directed against a medically relevant target, the coxsackievirus B3. We systematically analyzed the impact of different siRNA modification patterns and observed good compatibility of th...

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Bibliographic Details
Published in:FEBS letters 2010-02, Vol.584 (3), p.591-598
Main Authors: Werk, Denise, Wengel, Jesper, Wengel, Suzy L., Grunert, Hans-Peter, Zeichhardt, Heinz, Kurreck, Jens
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - pharmacology
Cercopithecus aethiops
Coxsackievirus
Coxsackievirus B3
Enterovirus B, Human - drug effects
Enterovirus B, Human - genetics
Heart - virology
Locked nucleic acid
Nucleic Acids - chemistry
RNA interference
RNA, Small Interfering - chemistry
RNA, Small Interfering - genetics
RNA, Small Interfering - pharmacology
Small interfering RNAs
Unlocked nucleic acid
Vero Cells
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Summary:This study describes the first application of unlocked nucleic acid (UNA)-modified small interfering RNAs (siRNAs) directed against a medically relevant target, the coxsackievirus B3. We systematically analyzed the impact of different siRNA modification patterns and observed good compatibility of the introduction of UNA with the maintenance of high antiviral activity. Additionally, the polarity of an siRNA was successfully reversed by modulating the relative stability of the termini with locked nucleic acid (LNA) and UNA as shown in a reporter assay. The potency of the reversed siRNA against the full-length target was, however, too low to inhibit the infectious virus. Altogether, combined modification of siRNAs with LNA und UNA provides a promising approach to alter and improve properties of an siRNA.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2009.12.007