Modulating viral gene expression by aptamers to RNA structures

Biol Cell. 2003 May-Jun;95(3-4):229-38. doi: 10.1016/s0248-4900(03)00036-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Viral / genetics*
  • HIV Long Terminal Repeat / genetics
  • Hepacivirus / genetics
  • Hepacivirus / metabolism
  • Humans
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Protein Biosynthesis / genetics*
  • Protein Structure, Tertiary / genetics
  • RNA, Viral / genetics*
  • Viral Proteins / biosynthesis*
  • Viral Proteins / genetics

Substances

  • Oligonucleotides
  • RNA, Viral
  • Viral Proteins