Chimeric bifunctional oligonucleotides as a novel tool to invade telomerase assembly

Dulat Azhibek, Maria Zvereva, Timofei Zatsepin, Maria Rubtsova, Olga Dontsova

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    Telomerase is a key participant in the telomere length maintaining system in eukaryotic cells. Telomerase RNA and protein reverse transcriptase subunits are essential for the appearance of active telomerase in vitro. Telomerase is active in many cancer types and is a potential target for anticancer drug development. Here we report a new approach for impairing telomerase function at the stage of human telomerase assembly. The approach is based on the application of chimeric bifunctional oligonucleotides that contain two oligonucleotide parts complementary to the functional domains of telomerase RNA connected with non-nucleotide linkers in different orientations (5′-3′, 5′-5′ or 3′-3′). Such chimeras inhibited telomerase in vitro in the nM range, but were effective in vivo in sub-nM concentrations, predominantly due to their effect on telomerase assembly and dimerization.

    Original languageEnglish
    Pages (from-to)9531-9542
    Number of pages12
    JournalNucleic Acids Research
    Volume42
    Issue number15
    DOIs
    Publication statusPublished - 2014

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