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 journalLetterResearchpeer-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

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Oligonucleotides
Nucleic acids
Vascular Endothelial Growth Factor A
Nucleotide Aptamers
Vascular Endothelial Growth Factor Receptor
Cell proliferation
Nucleotides
Molecular dynamics
DNA
Cells
Computer simulation
locked nucleic acid

Cite this

Edwards, S. L., Poongavanam, V., R Kanwar, J., Roy, K., M. Hillman, K., Prasad, N., ... Veedu, R. N. (2015). Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition. Chemical Communications, 51(46), 9499-9502. https://doi.org/10.1039/c5cc02756j
Edwards, Stacey L ; Poongavanam, Vasanthanathan ; R Kanwar, Jagat ; Roy, Kislay ; M. Hillman, Kristine ; Prasad, Neerati ; Leth-Larsen, Rikke ; Petersen, Michael ; Marusic, Maja ; Plavec, Janez ; Wengel, Jesper ; Veedu, Rakesh N. / Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition. In: Chemical Communications. 2015 ; Vol. 51, No. 46. pp. 9499-9502.
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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.",
author = "Edwards, {Stacey L} and Vasanthanathan Poongavanam and {R Kanwar}, Jagat and Kislay Roy and {M. Hillman}, Kristine and Neerati Prasad and Rikke Leth-Larsen and Michael Petersen and Maja Marusic and Janez Plavec and Jesper Wengel and Veedu, {Rakesh N.}",
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Edwards, SL, Poongavanam, V, R Kanwar, J, Roy, K, M. Hillman, K, Prasad, N, Leth-Larsen, R, Petersen, M, Marusic, M, Plavec, J, Wengel, J & Veedu, RN 2015, 'Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition', Chemical Communications, vol. 51, no. 46, pp. 9499-9502. https://doi.org/10.1039/c5cc02756j

Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition. / Edwards, Stacey L; Poongavanam, Vasanthanathan; R Kanwar, Jagat; Roy, Kislay; M. Hillman, Kristine; Prasad, Neerati; Leth-Larsen, Rikke; Petersen, Michael; Marusic, Maja; Plavec, Janez; Wengel, Jesper; Veedu, Rakesh N.

In: Chemical Communications, Vol. 51, No. 46, 07.05.2015, p. 9499-9502.

Research output: Contribution to journalLetterResearchpeer-review

TY - JOUR

T1 - Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition

AU - Edwards, Stacey L

AU - Poongavanam, Vasanthanathan

AU - R Kanwar, Jagat

AU - Roy, Kislay

AU - M. Hillman, Kristine

AU - Prasad, Neerati

AU - Leth-Larsen, Rikke

AU - Petersen, Michael

AU - Marusic, Maja

AU - Plavec, Janez

AU - Wengel, Jesper

AU - Veedu, Rakesh N.

PY - 2015/5/7

Y1 - 2015/5/7

N2 - 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.

AB - 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.

U2 - 10.1039/c5cc02756j

DO - 10.1039/c5cc02756j

M3 - Letter

C2 - 25968110

VL - 51

SP - 9499

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JO - Chemical Communications

JF - Chemical Communications

SN - 1359-7345

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Edwards SL, Poongavanam V, R Kanwar J, Roy K, M. Hillman K, Prasad N et al. Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition. Chemical Communications. 2015 May 7;51(46):9499-9502. https://doi.org/10.1039/c5cc02756j