Inhibition of HSV-1 ocular infection with morpholino oligomers targeting ICP0 and ICP27
Autor: | Ling Jin, Kathleen Eide, Robert E. Blouch, Robert J. Bildfell, Patrick L. Iversen, David A. Stein, Megan Moerdyk-Schauwecker |
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Rok vydání: | 2009 |
Předmět: |
Morpholino
medicine.drug_class Morpholines Ubiquitin-Protein Ligases viruses Molecular Sequence Data Acyclovir Herpesvirus 1 Human Drug resistance Virus Replication medicine.disease_cause Antiviral Agents Herpesviridae Virus Immediate-Early Proteins Morpholinos Mice Viral Proteins Virology Alphaherpesvirinae Chlorocebus aethiops Drug Resistance Viral medicine Animals Humans Vero Cells Pharmacology Base Sequence biology biology.organism_classification In vitro Keratitis Herpetic Vero cell Antiviral drug |
Zdroj: | Antiviral Research. 84:131-141 |
ISSN: | 0166-3542 |
Popis: | Alternative therapies are needed for HSV-1 infections in patients refractory to treatment with Acyclovir (ACV) and its derivatives. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded DNA analogues that enter cells readily and reduce target gene expression through steric blockage of complementary RNA. When applied before or soon after infection PPMO targeting the translation-start-site regions of HSV-1 ICP0 or ICP27 mRNA reduced HSV-1 plaque formation by 70-98% in vitro. The ICP0 PPMO also reduced ACV-resistant HSV-1 (strain 615.9) plaque formation by 70-90%, while an equivalent dose of ACV produced only 40-50% inhibition when the treatment was applied between 1 and 3hpi. Seven daily topical treatments of 100microg ICP0 PPMO caused no gross or microscopic damage to the corneas of uninfected mice. Topical application of 10microg ICP0 PPMO to the eyes of HSV-1 infected mice reduced the incidence of eye disease by 37.5-50% compared to controls. This study demonstrates that topically applied PPMO holds promise as an antiviral drug candidate against HSV-1 ocular infection. |
Databáze: | OpenAIRE |
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