REVIEW: Oligonucleotide Inhibitors of Telomerase: Prospects for Anticancer Therapy and Diagnostics

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M. I. Zvereva^1,2, T. S. Zatsepin^1,3, D. M. Azhibek³, O. S. Shubernetskaya^1,3, O. V. Shpanchenko^1*, and O. A. Dontsova^1,2

¹Lomonosov Moscow State University, Chemistry Faculty, 119991 Moscow, Russia; E-mail: olgash@genebee.msu.ru

²Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991 Moscow, Russia

³Skolkovo Institute of Science and Technology, ul. Novaya 100, 143025 Skolkovo, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received October 23, 2014; Revision received November 14, 2014

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The activity of telomerase allows eukaryotic cells to have unlimited division potential. On its functioning, telomerase synthesizes short DNA repeats at the 3′-end of DNA within chromosomes that ensures genome stability during cell division. Telomerase is active in the majority of cancer cell types and is virtually absent in somatic cells with rare exceptions. This difference allows us to consider inhibition of telomerase activity as a possible approach to antitumor therapy. Telomerase is a nucleoprotein composed of two main components: the reverse transcriptase (hTERT), which is a catalytic subunit, and telomerase RNA (hTR), which encodes a template for synthesis of repeats. The biogenesis and features of telomerase seem very promising for its inhibition due to complementary interactions. In this review, we analyze putative pathways of oligonucleotide influence on telomerase and consider the known native and modified oligonucleotide inhibitors of telomerase, as well as possible mechanisms of their action. We also discuss the application of telomerase-targeted oligonucleotide conjugates for in vivo imaging of tumor cells.

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KEY WORDS: human telomerase, telomerase inhibitors, anticancer therapy target, oligonucleotide, tumor cell imaging

DOI: 10.1134/S0006297915030013

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