The data obtained in the cell culture and suckling mice assays demonstrated that siRNA targeted to conserved regions of the FMDV genome could be effective against FMDV in either a specific or a cross-inhibitory manner. The potential of RNAi as an antiviral strategy against FMDV in relevant animal systems is of great interest. The fact that attenuated Salmonella is widely used as a DNA vaccine vector made us choose it as the vector for siRNA delivery. To test the anti-FMDV potential of rS. cho, we challenged guinea pigs pretreated by intramuscular injection of rS. cho constructs with FMDV HKN/2002. All saline-treated animals developed the major clinical sign of FMD, the appearance of vesicles on the feet, within 48 h of challenge (Tab. I). Guinea pigs treated with pLacZ/S. cho were not protected at all, though the clinical signs were delayed in some animals, as shown in Table I . However, 4 of 5 guinea pigs pretreated with 10 9 CFU of p3D-NT56/S. cho and challenged with 50 ID 50 of HKN/2002 developed none of the clinical signs such as vesicles or high fever. These results indicated that S. cho-delivered siRNA exerted in vivo inhibitory activity against FMDV in guinea pigs.