Edwards Stacey L, Poongavanam Vasanthanathan, Kanwar Jagat R, Roy Kislay, Hillman Kristine M, Prasad Neerati, Leth-Larsen Rikke, Petersen Michael, Marušič Maja, Plavec Janez, Wengel Jesper, Veedu Rakesh N
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072, Australia.
Chem Commun (Camb). 2015 Jun 11;51(46):9499-502. doi: 10.1039/c5cc02756j. Epub 2015 May 13.
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.
在本研究中，我们研究了一种名为RNV66的靶向血管内皮生长因子（VEGF）的锁核酸（LNA）修饰的DNA适配体对各种乳腺癌细胞系的疗效。我们的结果表明，RNV66在体外和体内均能有效抑制乳腺癌细胞增殖。引入LNA核苷酸对于提高疗效至关重要。此外，利用分子动力学模拟研究了RNV66与VEGF的结合相互作用，从而得到了LNA适配体-VEGF复合物阻断其与VEGF受体相互作用的首个计算模型。
