| Autor: |
David A. Stein, Claire Y.-H. Huang, Shawn Silengo, Adams Amantana, Stacy Crumley, Robert E. Blouch, Patrick L. Iversen, Richard M. Kinney, Stein, David A, Huang, Claire Y-H, Silengo, Shawn, Amantana, Adams, Crumley, Stacy, Blouch, Robert E, Iversen, Patrick L, Kinney, Richard M |
| Předmět: |
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| Zdroj: |
Journal of Antimicrobial Chemotherapy (JAC); Sep2008, Vol. 62 Issue 3, p555-555, 1p |
| Abstrakt: |
Objectives: 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).Methods: 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.Results: 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.Conclusions: 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] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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