As an antiviral technology, RNAi has already been widely researched for use with FMDV [5, 24, 33] . However, establishing RNAi as a viable approach to prevent FMDV requires resolving at least one major issue [17, 20] : the high genetic variability of FMD viruses. RNAi directed toward specific gene sequences of certain FMDV strains may face risks, especially in the event of an emergent FMD outbreak, because no information about the serotype or genotype of the isolated pathogen would be available while early protection is needed. Therefore, it may be necessary to design several siRNA that focus on the conserved regions of the viral genome [16, 17, 42, 46] . Previously, we showed that siRNA generated in vitro can effectively inhibit the replication of FMDV in either a specific or cross-inhibitory manner [28] . Another crucial issue that needs to be addressed is the optimal vector for delivery of siRNA-expressing cassettes. Chen et al. [6] demonstrated that treatment with recombinant, replication-defective human adenovirus type 5 expressing short-hairpin RNA significantly reduces the susceptibility of guinea pigs and swine to FMDV infection. However, adenovirus VA1 non-coding RNA is able to inhibit the biogenesis of siRNA and microRNA [30] . This finding suggests that novel siRNA delivery systems would be necessary.