Virological effects of ISIS 14803, an antisense oligonucleotide inhibitor of hepatitis C virus (HCV) internal ribosome entry site (IRES), on HCV IRES in chronic hepatitis C patients and examination of the potential role of primary and secondary HCV resistance in the outcome of treatment

• Published in: Antiviral therapy 2004-12, Vol.9 (6), p.953-968
• Main Authors: SOLER, Muriel, MCHUTCHISON, John G, KWOH, T. Jesse, DORR, F. Andrew, PAWLOTSKY, Jean-Michel
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions - genetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Base Sequence; Biological and medical sciences; Drug Resistance, Viral; Evolution, Molecular; Hepacivirus - classification; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; Medical sciences; Molecular Sequence Data; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - metabolism; Oligonucleotides, Antisense - pharmacology; Oligonucleotides, Antisense - therapeutic use; Pharmacology. Drug treatments; RNA, Viral - genetics; RNA, Viral - metabolism; Sequence Analysis, DNA; Treatment Outcome; Viral Load
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350400900612

Antisense oligonucleotides represent a promising class of antiviral agents. ISIS 14803 is a 20-unit phosphorothioate oligodeoxynucleotide that inhibited hepatitis C virus (HCV) replication and protein expression in cell culture and mouse models. A Phase I dose-escalation clinical study of ISIS 14803 was performed in 24 patients with HCV genotype 1 chronic hepatitis C. The patients received 0.5, 1.0, 2.0 or 3.0 mg/kg of ISIS 14803 for 4 weeks. Two of them receiving 2.0 mg/kg, experienced a significant (>1.0 log10) viral load reduction and nine other patients experienced minor (