Quick identification of effective small interfering RNAs that inhibit the replication of coxsackievirus A16

Coxsackievirus A16 (CA16) is a major causative agent of hand, foot, and mouth disease (HFMD). It can cause myocarditis, pericarditis and fatal shock. There is no effective therapy against CA16. RNA interference (RNAi) is a powerful tool to silence gene expression. The small interfering RNA (siRNA) that induces RNA degradation has recently been used as an anti-virus agent to inhibit virus replication. In this study, we established the complete nucleotide sequence of CA16 strain Shzh05-1, and then compared the nucleotide sequences of Shzh05-1 with sequences of other CA16 strains in GenBank. We chose conserved regions between Shzh05-1 and the two other CA16 strains to design 30 siRNAs and construct siRNA-encoding plasmids. Thirteen siRNAs targeting conserved regions of the virus could effectively block replication of CA16 in cultured cells. Combination transfection of these 13 effective siRNAs could also produce a high inhibitory effect. These strategies and results suggest that RNAi has potential therapeutic use for suppression of CA16 infection. (C) 2008 Elsevier B.V. All rights reserved.