Modulating viral gene expression by aptamers to RNA structures.
Oligonucleotides exhibiting a strong affinity and a high specificity for RNA hairpins were obtained by in vitro selection. Such oligomers give rise to loop-loop complexes with the target hairpins: the trans-activation responsive (TAR) element of the Human Immunodeficiency virus-1 (HIV-1) or subdomains of the Hepatitis C virus (HCV) mRNA. Chemically modified derivatives of an antiTAR aptamer were shown to compete out the binding of the viral protein Tat and to selectively inhibit the in vitro TAR-dependent transcription of a reporter gene. In addition, antisense oligomers derived from sequences selected against the domain IIId of the HCV internal ribosome entry site were shown to specifically block translation both in a cell-free assay and in cultured cells.
Toulmé
Jean-Jacques
JJ
Inserm U386, IFR 66, Université Victor-Segalen, 146, rue Léo-Saignat, 33076 Bordeaux cedex 2, France. jean-jacques.toulme@bourdeaux.inserm.fr
Darfeuille
Fabien
F
Kolb
Gaëlle
G
Chabas
Sandrine
S
Staedel
Cathy
C
D000818:Animals; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics*; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
D009841:Oligonucleotides; D012367:RNA, Viral; D014764:Viral Proteins