Comparative studies of tricyclo-DNA- and LNA-containing oligonucleotides as inhibitors of HIV-1 gene expression
- PMID: 18066894
- DOI: 10.1080/15257770701490928
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.
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