Delivery of double-stranded DNA thioaptamers into HIV-1 infected cells for antiviral activity

Monique R. Ferguson, Daniel R. Rojo, Anoma Somasunderam, Varatharasa Thiviyanathan, Bettye D. Ridley, Xianbin Yang, David G. Gorenstein

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Oligonucleotide agents (ODN) are emerging as attractive alternatives to chemical drugs. However, the clinical use of ODNs as therapeutics has been hindered by their susceptibility to degradation by cellular enzymes and their limited ability to penetrate intact cells. We have used various liposome-mediated transfection agents, for the in vitro delivery of DNA thioaptamers into U373-MAGI-CCR5 cells. Our lead thioaptamer, R12-2, targets the RNase H domain of the HIV-1 reverse transcriptase (RT) and inhibits viral infection in U373-MAGI-CCR5 cells. R12-2, a 62-base-pair, double-stranded DNA molecule with a monothio-phosphate modified backbone, was selected through a novel combinatorial selection method. We studied the use of oligofectamine (OF), TFX-20, Transmessenger (TM), and Gene Jammer (GJ) for transfection of the thio-modified DNA aptamers. OF-transfected U373-MAGI-CCR5 cells resulted in 68% inhibition of HIV infection in the treated cells compared to the untreated control. Inhibition was observed in a dose-dependent manner with maximal inhibition of 83%. In this report, we demonstrate that monothioate-modified DNA duplex oligonucleotides can be efficiently delivered into cells by liposome-based transfection agents to inhibit HIV replication.

Original languageEnglish (US)
Pages (from-to)792-797
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume344
Issue number3
DOIs
StatePublished - Jun 9 2006

Keywords

  • HIV
  • Liposomes
  • Oligonucleotide
  • RNase H
  • RT inhibitors
  • Thioaptamer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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