Antisense oligonucleotide inhibition of hepatitis C virus (HCV) gene expression in livers of mice infected with an HCV-vaccinia virus recombinant
| Autor: | R F Azad, Boyd Conklin, Ronnie C. Hanecak, M C Fox, Vickie L. Brown-Driver, Hong Zhang, Kevin P. Anderson |
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| Rok vydání: | 1999 |
| Předmět: |
Gene Expression Regulation
Viral Hepatitis C virus Genetic Vectors Codon Initiator Vaccinia virus Cytidine Hepacivirus medicine.disease_cause Recombinant virus Antiviral Agents Virus Viral vector chemistry.chemical_compound Mice medicine Animals Pharmacology (medical) Poxviridae Orthopoxvirus Luciferases Conserved Sequence Pharmacology Recombination Genetic Mice Inbred BALB C biology Dose-Response Relationship Drug Oligonucleotides Antisense biology.organism_classification Virology Molecular biology Hepatitis C Internal ribosome entry site Infectious Diseases Phenotype chemistry Liver Female Vaccinia |
| Zdroj: | Antimicrobial agents and chemotherapy. 43(2) |
| ISSN: | 0066-4804 |
| Popis: | Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. Current treatments are not curative for most infected individuals, and there is an urgent need for both novel therapeutic agents and small-animal models which can be used to evaluate candidate drugs. A small-animal model of HCV gene expression was developed with recombinant vaccinia virus vectors. VHCV-IRES (internal ribosome entry site) is a recombinant vaccinia viral vector containing the HCV 5′ nontranslated region (5′-NTR) and a portion of the HCV core coding region fused to the firefly luciferase gene. Intraperitoneal injection of VHCV-IRES produced high levels of luciferase activity in the livers of BALB/c mice. Antisense oligonucleotides complementary to the HCV 5′-NTR and translation initiation codon regions were then evaluated for their effects on the expression of these target HCV sequences in BALB/c mice infected with the vaccinia virus vector. Treatment of VHCV-IRES-infected mice with 20-base phosphorothioate oligonucleotides complementary to the sequence surrounding the HCV initiation codon (nucleotides 330 to 349) specifically reduced luciferase expression in the livers in a dose-dependent manner. Inhibition of HCV reporter gene expression in this small-animal model suggests that antisense oligonucleotides may provide a novel therapy for treatment of chronic HCV infection. |
| Databáze: | OpenAIRE |
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