Key result
siLNA targeting coxsackievirus B3 improves infected cell viability by ~92% and exerts good antiviral activity.
Why the study?
The highly structured 5' UTR of coxsackievirus B3 is an attractive conserved target for antiviral siRNA development, but effective targeting strategies are needed.
LNA-modified siRNAs targeting the highly structured 5' UTR of coxsackievirus B3 demonstrate significant antiviral activity and improve infected cell viability in vitro.
LNA-siRNA design strategy for CVB-3 requires in vivo validation; leaves open therapeutic RNAi in viral myocarditis.
This study describes a strategy to develop LNA-modified small interfering RNA (siRNAs) against the highly structured 5' UTR of coxsackievirus B3 (CVB-3), which is an attractive target site due to its high degree of conservation. Accessible sites were identified based on structural models and RNase H assays with DNA oligonucleotides. Subsequently, LNA gapmers, siRNAs, siLNAs and small internally segmented interfering RNA (sisiLNAs) were designed against sites, which were found to be accessible in the in vitro assays, and tested in reporter assays and experiments with the infectious virus. The best siLNA improved viability of infected cells by 92% and exerted good antiviral activity in plaque reduction assays.
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Dutkiewicz et al. (2008) studied Coxsackievirus B3 (CVB-3) infection. LNA-modified siRNAs (siLNAs) was evaluated on Viability of infected cells. The best siLNA against the 5' UTR of coxsackievirus B3 improved the viability of infected cells by 92% and exerted good antiviral activity in plaque reduction assays.
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