Antitumor activity of small double-stranded oligodeoxynucleotides targeting telomerase RNA in malignant melanoma

Faiza Noreen1, Jochen Heinrich, Karin Moelling

  • 1Institute of Medical Virology, University of Zurich, Zurich, Switzerland.

Oligonucleotides
|May 16, 2009
PubMed

Insights

Partially double-stranded oligodeoxynucleotides (ODNs) effectively inhibited human telomerase RNA (hTR) and mouse telomerase RNA (mTR), reducing cancer cell proliferation and metastasis in vivo.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Oligonucleotide Therapeutics

Background:

  • Human telomerase RNA (hTR) is a key component of the telomerase enzyme.
  • Previous studies utilized small interfering RNAs (siRNAs) and antisense oligonucleotides for hTR silencing.

Purpose of the Study:

  • To evaluate the efficacy of partially double-stranded oligodeoxynucleotides (ODNs) against hTR and mouse telomerase RNA (mTR).
  • To compare ODN performance with single-stranded antisense ODNs and siRNAs in vitro and in vivo.

Main Methods:

  • ODNs were designed to target hTR in HeLa cells and mTR in B16-F10 cells.
  • In vitro inhibition, cell proliferation, apoptosis, and RNase H contribution were assessed.
  • In vivo efficacy was evaluated by administering ODN-transfected B16-F10 cells to C57BL/6 mice.

Main Results:

  • ODNs achieved 68% inhibition of hTR and 81% inhibition of mTR.
  • ODN treatment rapidly inhibited cell proliferation and induced apoptosis.
  • A 70% reduction in lung metastases was observed after intravenous ODN administration in mice.
  • RNase H activity was implicated in hTR inhibition.

Conclusions:

  • Partially double-stranded ODNs represent a novel class of nucleic acids for telomerase-based antiproliferative strategies.
  • These ODNs demonstrate significant potential for cancer treatment by targeting telomerase RNA.

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