Morpholino oligomers are single stranded anti-sense molecules that exert their action by steric blocking of complementary RNA. Unlike other types of anti-sense oligonucleotides, Morpholinos provide all the desired properties of stability, nuclease resistance, high efficacy, long-term activity, water solubility, low toxicity, and exquisite specificity. Morpholino oligomers has been used previously for the inhibition of flaviviral replication [14, 27] including JEV [15] though all of them has utilized peptide based Morpholinos. The peptide based Morpholinos contain delivery moiety evolved from natural peptides whose active components are 6-9 arginine residues in a bio-available 6-aminohexanoicspaced structure [28] . However, these arginine-based peptides are not commercially available for research purposes and their greatest efficacies have been in delivering Morpholinos to the cytosol of tissues like liver [29] or leaky muscle [30] , which would be considered as easily deliverable. As a result, the reach of peptide based Morpholinos into a wide spectrum of tissues remains questionable [18] . Also, owing to the peptidic nature, degradation of the peptide portion of the conjugates was found to be time and tissue dependent [31] . Furthermore, the applications of the arginine-rich peptide transporters are limited due to their high cost, scalability and stability. Added to that are the risks of immune responses against the peptides which limits repeated administrations for diseases requiring long-term treatment [32] . Increases were observed in the ROS levels in the brain samples of JEVinfected and JEV+SC-MO groups in comparison to Sham, that were reduced following 39 and 59 MO treatments. Although ROS levels were decreased in JEV+39 MO group when compared to JEV-infected group, it remained significantly higher than that in Sham (A). Approximately 13-fold increases were observed in the levels of HSP-70 in JEV-infected and JEV+SC-MO groups as compared to Sham. These drastic increases were significantly reduced in JEV+39 MO and JEV+59 MO groups, the levels remained significantly higher than Sham (B&C). SOD-1 levels were found to be elevated 2and nearly 3-fold in JEV-infected and JEV+SC-MO groups respectively compared to Sham. 39 and 59 MO treatment caused significant reduction of SOD-1 levels compared to JEV-infected group (B&D). Alterations in TRX-1 levels were similar to that observed in SOD-1 except that its level in JEV+ SC-MO was not significantly different than only JEV-infected group (B&E). Nearly 2-fold increases were observed in NO levels of JEV-infected and JEV+SC-MO groups when compared to those obtained from Sham. NO levels were subsequently reduced to significantly lower levels following 39 and 59MO treatments (F). iNOS expression was found to increase 8-fold in JEV-infected and JEV+SC-MO groups when compared to Sham. Following 39 and 59MO treatments iNOS levels decreased significantly as compared to JEV-infected group (G&H). ( * p,0.01 for JEV when compared to Sham; ** p,0.01 for JEV+SC-MO when compared to JEV-infected only; # p,0.01 for JEV+ 39MO To minimize the problems encountered by the peptideconjugated Morpholinos, octaguanidinium dendrimer-conjugated Morpholino oligomers have been developed that are commonly referred to as Vivo-Morpholino (MO). These custom-sequence anti-sense molecules have been reported to enable Morpholino applications in adult animals. MO was our choice of anti-sense molecule as this enabled us to test the specifically designed oligonucleotides in both animal as well as cell culture models. Though 'outstanding' results have been reported to be achieved by intravenous (i.v.) administration of the MO, we preferred the intraperitoneal route via which modest systemic delivery can be achieved. This was so done because brain has been reported to be an ineffective tissue when MOs are administered i.v. [33] , though there is no direct evidence showing that MOs can cross blood brain barrier, when administered via other routes. According to the manufacturer's (Gene Tools LLC) instructions the maximum suggested dosage in mammals is 12.5 mg/kg in a 24 hour period. Our aim was to determine the minimum dose at which our desired effects could be achieved. Initially we had chosen two doses of 5 mg and 10 mg per kg body weight (b.w.) of the animals. We found that there was no significant difference between the survival rate of JEV-infected and MO treated mice in either dose (data not shown for 10 mg/kg b.w.). The survival rate was approximately 90% in those JEV-infected animals that were treated with 39 MO and 75% in animals treated with 59 MO. Thus we decided to proceed with the 5 mg/kg b.w. dose for all subsequent experiments.