Anti-HCV RNA Aptamers Targeting the Genomic cis-Acting Replication Element

Pharmaceuticals

Soledad Marton¹  Beatriz Berzal-Herranz¹  Eva Garmendia¹  Francisco J. Cueto¹ 

[1] Instituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, P.T. Ciencias de la Salud, Av. del Conocimiento s/n, Armilla, 18100 Granada, Spain;

关键词: aptamer selection;    SELEX;    RNA aptamers;    anti-HCV aptamers;    aptamer therapeutics;   

DOI  :  10.3390/ph5010049

来源: mdpi

【 摘 要 】

Hepatitis C virus (HCV) replication is dependent on the existence of several highly conserved functional genomic RNA domains. The cis-acting replication element (CRE), located within the 3' end of the NS5B coding region of the HCV genome, has been shown essential for efficient viral replication. Its sequence and structural features determine its involvement in functional interactions with viral RNA-dependent RNA polymerase and distant RNA domains of the viral genome. This work reports the use of an in vitro selection strategy to select aptamer RNA molecules against the complete HCV-CRE. After six selection cycles, five potential target sites were identified within this domain. Inhibition assays using a sample of representative aptamers showed that the selected RNAs significantly inhibit the replication (>80%) of a subgenomic HCV replicon in Huh-7 cell cultures. These results highlight the potential of aptamer RNA molecules as therapeutic antiviral agents.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.