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Treatment of AG129 mice with antisense morpholino oligomers increases survival time following challenge with dengue 2 virus.
- Source :
-
Journal of Antimicrobial Chemotherapy (JAC) . Sep2008, Vol. 62 Issue 3, p555-555. 1p. - Publication Year :
- 2008
-
Abstract
- <bold>Objectives: </bold>To determine the antiviral activity of phosphorodiamidate morpholino oligomers (PMO) and peptide-conjugated PMO (PPMO) in AG129 mice infected with dengue 2 virus (DENV-2).<bold>Methods: </bold>Antisense PMO and PPMO were designed against the 5' terminal region (5'SL) or the 3'-cyclization sequence region (3'CS) of DENV genomic RNA and administered to AG129 mice before and/or after infection with DENV-2. In addition, cell culture evaluations designed to determine optimum PPMO length, and pharmacokinetic and toxicity analysis of PPMO were also carried out.<bold>Results: </bold>Mock-treated AG129 mice lived for 9-17 days following intraperitoneal (ip) infection with 10(4)-10(6) pfu of DENV-2 (strain New Guinea C). Intraperitoneal administration of 5'SL or 3'CS PPMO before and after DENV infection produced an increase in the average survival time of up to 8 days. Animals receiving only post-infection PPMO treatment did not benefit significantly. Cell culture studies showed that PPMO of 22-24 bases long produced substantially higher DENV titre reductions than did PPMO that were either shorter or longer. Pharmacokinetic and toxicology analysis with non-infected animals showed that nine consecutive once-daily ip treatments of 10 mg/kg PPMO resulted in high concentrations of PPMO in the liver and caused little impact on overall health.<bold>Conclusions: </bold>The data indicate that PPMO had considerable antiviral efficacy against DENV-2 in the AG129 mouse model and that PPMO treatment early in the course of an infection was critical to extending the survival times of DENV-2-infected mice in the AG129 model system. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GEL permeation chromatography
*CHROMATOGRAPHIC analysis
*SEPHAROSE
*RODENTS
Subjects
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 62
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 34010043
- Full Text :
- https://doi.org/10.1093/jac/dkn221