title: Three properties of the hepatitis C virus RNA genome related to antiviral strategies based on RNA-therapeutics: variability, structural conformation and tRNA mimicry.
abstract: 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.
authors.affiliation: Servicio de Medicina Interna-Hepatología, Hospital Universitari Vall d'Hebron, Universitat Autónoma de Barcelona, 08035 Barcelona, Spain. jgomez@vhebron.net
authors.forename: Jordi
authors.initials: J
authors.lastname: Gómez
authors.forename: Anna
authors.initials: A
authors.lastname: Nadal
authors.forename: Rosario
authors.initials: R
authors.lastname: Sabariegos
authors.forename: Nerea
authors.initials: N
authors.lastname: Beguiristain
authors.forename: María
authors.initials: M
authors.lastname: Martell
authors.forename: Maria
authors.initials: M
authors.lastname: Piron
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D018390:Gene Targeting; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000628:therapy; D006801:Humans; D018716:Molecular Mimicry; D011487:Protein Conformation; D034622:RNA Interference; D016337:RNA, Catalytic / Q000235:genetics; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D016337:RNA, Catalytic; D012367:RNA, Viral; D012343:RNA, Transfer