Modulating viral gene expression by aptamers to RNA structures

Abstract

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.

SELEX—A (r)evolutionary method to generate high-affinity nucleic acid ligands

“…By interfering biological processes mediated by tertiary RNA structures, e.g. in pathogens, these aptamers could also function as therapeutic oligonucleotides (Duconge and Toulme, 1999;Toulme et al, 2003). According to the ratio among the publications concerning aptamers, most of the aptamers were selected for proteins or for peptides as special epitopes of a protein of interest.…”

Functional Aptamers and Aptazymes in Biotechnology, Diagnostics, and Therapy

“…Progress on this relatively new approach has been reviewed recently. 298 Generation of aptamers targeting essential nucleic acid structures complements established techniques such as ribozymes and antisense and RNA interference technologies. The advantage of using aptamers rather than the approaches mentioned above is that highly structured target sites can potentially be targeted.…”

DNA and RNA Aptamers: From Tools for Basic Research Towards Therapeutic Applications

“…A specific anti-TAR aptamer selected to inhibit the interaction of TAR with Tat displayed antiviral properties in tissue culture. Following chemical modifications, the aptamer blocked TAR binding to Tat and selectively inhibited in vitro TAR-dependent transcription of a reporter gene [71]. Viruses must specifically interact with host cell membrane proteins during infection.…”