Three Properties of the Hepatitis C Virus RNA Genome Related to Antiviral Strategies Based on RNA-Therapeutics: Variability, Structural Conformation and tRNA Mimicry
The concept of using RNA molecules as therapeutic agents is receiving increasing attention by basic science and pharmaceutical research. Over the past five years, a number of clinical trials have been initiated to evaluate the efficacy and safety of several RNA agents for the treatment of a range of conditions from cancer to infectious disease. From a molecular biology perspective, two main factors are implicated in RNA therapeutics against pathogenic RNAs: i / The activity, stability and delivery of the inactivating agent (ribozyme, RNase P, “decoy” RNA, aptamer, small interfering-RNA) and its co-localisation with the target; and ii / The properties of the RNA substrate, which, in the case of an RNA virus, most likely limit the effectiveness of the inactivating agent. The main reasons are the limited size of the viral genome and the restrictions imposed by the RNA structure and variations at the target.
In the first section of this article we review three properties of the HCV RNA genome, from primary sequence to tertiary structure, which imply restrictions and opportunities for RNA-based treatment. In the second section, we briefly describe several of the RNA-based therapeutic strategies against HCV now under development.
In the first section of this article we review three properties of the HCV RNA genome, from primary sequence to tertiary structure, which imply restrictions and opportunities for RNA-based treatment. In the second section, we briefly describe several of the RNA-based therapeutic strategies against HCV now under development.
Keywords: hepatitis c virus; ribozymes; rna targeting; rnase p; sirna; trna-like; viral quasispecies
Document Type: Review Article
Affiliations: Laboratorio Medicina Interna- Hepatologia, Area de investigacion B. Hospital Vall d'Hebron Passeig Vall d'Hebron 119-129 08035 Barcelona, Spain.
Publication date: 01 November 2004
- Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism. - Editorial Board
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