Intracranial Administration of P Gene siRNA Protects Mice from Lethal Chandipura Virus Encephalitis

Kumar, Satyendra; Arankalle, Vidya A.

Simultaneous administration of 5 mg P-2 siRNA and 100 or 10LD 50 virus resulted in 48 and 96 hr delay respectively in the appearance of symptoms and death (Fig 7a and b) . One mouse survived with the lower dose of the virus. Importantly, when two doses 5 mg P-2 siRNA were administered 24 hr apart, 70% mice survived. In this experiment, the first dose of siRNA was given simultaneously with the virus. To examine the degree of protection offered by siRNA when administered after the virus inoculation, a different two dose schedule was tried. i.e., 2 or 4 hr and 24hr-postvirus inoculation (Fig 11a and 11b) . Survival was reduced to 40% and 20% respectively. Considering the rapidity of CHPV replication, these results are significant. If we could introduce large amount of siRNA post-infection, survival of mice seems likely. Due to the limitation of the volume, this could not be tried. It is pertinent to note here that for JE virus, a single injection containing 40ug of siRNA with JetSI/DOPE led to complete protection [20] . We need to try different liposome formulations encapsulating optimum concentration of P-2 siRNA for achieving near 100% survival when administered after infection with the virus at variable intervals.