Key result
UNA-modified siRNAs maintain high antiviral activity against coxsackievirus B3 while reversed polarity siRNAs lack potency.
Why the study?
The application of UNA-modified siRNAs against the heart-pathogenic coxsackievirus B3 and their modification patterns had not been systematically analyzed.
Combined modification of siRNAs with LNA and UNA provides a promising approach to alter and improve siRNA properties against heart-pathogenic coxsackievirus B3.
UNA-compatible siRNA modifications sustain antiviral activity against coxsackievirus B3; hypothesis-generating for myocarditis therapies pending further validation.
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.
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Werk et al. (2009) studied Coxsackievirus B3 infection. Unlocked nucleic acid (UNA)-modified small interfering RNAs (siRNAs) was evaluated on Antiviral activity and inhibition of infectious virus. Unlocked nucleic acid (UNA)-modified small interfering RNAs maintained high antiviral activity against coxsackievirus B3, though reversed polarity siRNAs lacked sufficient potency to inhibit the virus.
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