An engineered inhibitor RNA that efficiently interferes with hepatitis C virus translation and replication.
Antiviral Res
; 94(2): 131-8, 2012 May.
Article
en En
| MEDLINE
| ID: mdl-22426470
Hepatitis C virus (HCV) translation is mediated by a highly conserved internal ribosome entry site (IRES), mainly located at the 5'untranslatable region (5'UTR) of the viral genome. Viral protein synthesis clearly differs from that used by most cellular mRNAs, rendering the IRES an attractive target for novel antiviral compounds. The engineering of RNA compounds is an effective strategy for targeting conserved functional regions in viral RNA genomes. The present work analyses the anti-HCV potential of HH363-24, an in vitro selected molecule composed of a catalytic RNA cleaving domain with an extension at the 3' end that acts as aptamer for the viral 5'UTR. The engineered HH363-24 efficiently cleaved the HCV genome and bound to the essential IIId domain of the IRES region. This action interfered with the proper assembly of the translationally active ribosomal particles 48S and 80S, likely leading to effective inhibition of the IRES function in a hepatic cell line. HH363-24 also efficiently reduced HCV RNA levels up to 70% in a subgenomic replicon system. These findings provide new insights into the development of potential therapeutic strategies based on RNA molecules targeting genomic RNA structural domains and highlight the feasibility of generating novel engineered RNAs as potent antiviral agents.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Biosíntesis de Proteínas
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Replicación Viral
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Productos Biológicos
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ARN Viral
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ARN Catalítico
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Hepacivirus
Límite:
Humans
Idioma:
En
Revista:
Antiviral Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Países Bajos