An RNA alternative to human transferrin: a new tool for targeting human cells.
An RNA alternative to human transferrin: a new tool for targeting human cells.
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DOI：
10.1038/mtna.2012.14
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发表时间：
2012-05-15
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--
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转铁蛋白受体，CD71，是一个有吸引力的药物开发的目标，因为它在许多癌细胞系和血脑屏障的高表达。为了产生识别人转铁蛋白受体的血清稳定的适体，我们通过采用富集结合靶受体并被细胞内化的RNA分子的功能性选择步骤来修改传统的适体选择方案。所选适体对人受体具有特异性，可迅速被细胞内吞，并具有共同的核心结构。发现最小化的变体与天然配体转铁蛋白竞争受体结合和细胞摄取，但在竞争实验中比其表现好两倍。使用这种分子，我们产生了适体靶向siRNA负载脂质体。与未修饰或非靶向脂质体相比，适体靶向增强了在培养中生长的细胞中的摄取和靶基因敲低。适体应证明在许多应用中作为转铁蛋白的替代物是有用的，包括细胞成像和靶向药物递送。
The transferrin receptor, CD71, is an attractive target for drug development because of its high expression on a number of cancer cell lines and the blood brain barrier. To generate serum-stabilized aptamers that recognize the human transferrin receptor, we have modified the traditional aptamer selection protocol by employing a functional selection step that enriches for RNA molecules which bind the target receptor and are internalized by cells. Selected aptamers were specific for the human receptor, rapidly endocytosed by cells and shared a common core structure. A minimized variant was found to compete with the natural ligand, transferrin, for receptor binding and cell uptake, but performed ~twofold better than it in competition experiments. Using this molecule, we generated aptamer-targeted siRNA-laden liposomes. Aptamer targeting enhanced both uptake and target gene knockdown in cells grown in culture when compared to nonmodified or nontargeted liposomes. The aptamer should prove useful as a surrogate for transferrin in many applications including cell imaging and targeted drug delivery.
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影响因子：
46.9
作者：
Dassie, Justin P.;Liu, Xiu-ying;Thomas, Gregory S.;Whitaker, Ryan M.;Thiel, Kristina W.;Stockdale, Katie R.;Meyerholz, David K.;McCaffrey, Anton P.;McNamara, James O., II;Giangrande, Paloma H.
通讯作者：
Giangrande, Paloma H.
影响因子：
4.7
作者：
Mendonca, Liliana S.;Firmino, Filipe;Simoes, Sergio
通讯作者：
Simoes, Sergio
影响因子：
4.8
作者：
Laske, DW;Muraszko, KM;Youle, RJ
通讯作者：
Youle, RJ
影响因子：
12.4
作者：
Magalhaes, Maria L. B.;Byrom, Michelle;Levy, Matthew
通讯作者：
Levy, Matthew
影响因子：
--
作者：
Collingwood, Michael A.;Rose, Scott D.;Behlke, Mark A.
通讯作者：
Behlke, Mark A.