title: Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition.
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.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072, Australia.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Edwards
authors.forename: Vasanthanathan
authors.initials: V
authors.lastname: Poongavanam
authors.forename: Jagat R
authors.initials: JR
authors.lastname: Kanwar
authors.forename: Kislay
authors.initials: K
authors.lastname: Roy
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Hillman
authors.forename: Neerati
authors.initials: N
authors.lastname: Prasad
authors.forename: Rikke
authors.initials: R
authors.lastname: Leth-Larsen
authors.forename: Michael
authors.initials: M
authors.lastname: Petersen
authors.forename: Maja
authors.initials: M
authors.lastname: Marušič
authors.forename: Janez
authors.initials: J
authors.lastname: Plavec
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
authors.forename: Rakesh N
authors.initials: RN
authors.lastname: Veedu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006147:Guanine; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008819:Mice, Nude; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009841:Oligonucleotides / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D009841:Oligonucleotides; C000605035:RNV66 DNA aptamer; D042461:Vascular Endothelial Growth Factor A; C477371:locked nucleic acid; D006147:Guanine