title: Comparative studies of tricyclo-DNA- and LNA-containing oligonucleotides as inhibitors of HIV-1 gene expression.
abstract: Trans-activation of HIV-1 transcription is triggered by the interaction of the protein Tat and host cellular factors with a 59-residue stem-loop RNA known as the trans-activation responsive element (TAR). Here we compare the trans-activation steric block inhibitory activity of 16-mer oligonucleotides targeted to TAR containing tricyclo-DNAs, and their mixmers with LNA or OMe residues, with LNA/OMe oligonucleotide. Despite generally weaker TAR RNA binding affinity, all tricyclo-DNA oligonucleotides showed similarly good activity levels to OMe/LNA oligonucleotide in a HeLa Tat-dependent trans-activation cell reporter assay with cationic lipid delivery, but mixmers of tricyclo-DNA were inactive. Tricyclo-DNA 16-mer showed sequence-specific inhibition of beta-galactosidase expression in an anti-HIV HeLa cell reporter assay.
authors: Laboratory of Molecular Biology, Medical Research Council, Cambridge, UK.
authors: Gabriela
authors: G
authors: Ivanova
authors: Andrey
authors: A
authors: Arzumanov
authors: Michael J
authors: MJ
authors: Gait
authors: Sandrine
authors: S
authors: Reigadas
authors: Jean-Jacques
authors: JJ
authors: Toulmé
authors: Marie-Line
authors: ML
authors: Andreola
authors: Damian
authors: D
authors: Ittig
authors: Christian
authors: C
authors: Leumann
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D038621:Regulatory Sequences, Ribonucleic Acid; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D009841:Oligonucleotides; D011083:Polycyclic Compounds; D038621:Regulatory Sequences, Ribonucleic Acid; D004247:DNA