Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition

Stacey L Edwards, Vasanthanathan Poongavanam, Jagat R Kanwar, Kislay Roy, Kristine M. Hillman, Neerati Prasad, Rikke Leth-Larsen, Michael Petersen, Maja Marusic, Janez Plavec, Jesper Wengel, Rakesh N. Veedu

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

In this study, we investigated the efficacy of an LNA (locked nucleic acid)-modified DNA aptamer named RNV66 targeting VEGF against various breast cancer cell lines. Our results demonstrate that RNV66 efficiently inhibits breast cancer cell proliferation both in vitro and in vivo. Introduction of LNA nucleotides were crucial for higher efficacy. Furthermore, the binding interaction of RNV66 with VEGF was investigated using molecular dynamic simulations leading to the first computational model of the LNA aptamer–VEGF complex blocking its interaction with VEGF-receptor.
Original languageEnglish
JournalChemical Communications
Volume51
Issue number46
Pages (from-to)9499-9502
ISSN1359-7345
DOIs
Publication statusPublished - 7. May 2015

Keywords

  • Animals
  • Antineoplastic Agents/chemistry
  • Aptamers, Nucleotide/chemistry
  • Breast Neoplasms/drug therapy
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Female
  • Guanine
  • Human Umbilical Vein Endothelial Cells/drug effects
  • Humans
  • Mice, Nude
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Oligonucleotides/chemistry
  • Tumor Burden/drug effects
  • Vascular Endothelial Growth Factor A/metabolism

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