Targeting Insulin Receptor with a Novel Internalizing Aptamer.
Targeting Insulin Receptor with a Novel Internalizing Aptamer.
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DOI：
10.1038/mtna.2016.73
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发表时间：
2016-09-20
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基于核酸的适体正在成为疾病相关蛋白如受体酪氨酸激酶的治疗性拮抗剂。它们是通过体外组合化学方法选择的，称为指数富集配体系统进化（SELEX），由于它们的小尺寸和独特的化学特性，它们在诊断和治疗方面具有优于抗体的几个优势。此外，快速内化到靶细胞中的适体也具有作为次级治疗剂的递送工具的体内用途的巨大潜力。在这里，我们描述了一种核酸酶抗性RNA适体，命名为GL56，它特异性地识别胰岛素受体（IR）。GL56通过基于细胞的SELEX方法分离，该方法允许富集内化适体，GL56快速内化到靶细胞中，并且能够区分IR与高度同源的胰岛素样生长因子受体1。值得注意的是，当应用于表达IR的癌细胞时，适体抑制IR依赖性信号传导。鉴于人们对胰岛素受体作为癌症治疗靶点的兴趣日益浓厚，GL56揭示了一种具有巨大翻译潜力的新型分子，可作为IR依赖性癌症的抑制剂和递送工具。
Nucleic acid-based aptamers are emerging as therapeutic antagonists of disease-associated proteins such as receptor tyrosine kinases. They are selected by an in vitro combinatorial chemistry approach, named Systematic Evolution of Ligands by Exponential enrichment (SELEX), and thanks to their small size and unique chemical characteristics, they possess several advantages over antibodies as diagnostics and therapeutics. In addition, aptamers that rapidly internalize into target cells hold as well great potential for their in vivo use as delivery tools of secondary therapeutic agents. Here, we describe a nuclease resistant RNA aptamer, named GL56, which specifically recognizes the insulin receptor (IR). Isolated by a cell-based SELEX method that allows enrichment for internalizing aptamers, GL56 rapidly internalizes into target cells and is able to discriminate IR from the highly homologous insulin-like growth factor receptor 1. Notably, when applied to IR expressing cancer cells, the aptamer inhibits IR dependent signaling. Given the growing interest in the insulin receptor as target for cancer treatment, GL56 reveals a novel molecule with great translational potential as inhibitor and delivery tool for IR-dependent cancers.
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影响因子：
5.2
作者：
Malaguarnera R;Belfiore A
通讯作者：
Belfiore A
DOI：
10.1038/mtm.2016.14
发表时间：
2016
期刊：
Molecular therapy. Methods & clinical development
影响因子：
--
作者：
Maier KE;Levy M
通讯作者：
Levy M
影响因子：
3.9
作者：
Sachdev, D;Yee, D
通讯作者：
Yee, D
影响因子：
3.1
作者：
Aljada, Ahmad;Saleh, Ayman M.;Ahmed, Altayeb Abdalla
通讯作者：
Ahmed, Altayeb Abdalla
DOI：
10.1007/978-1-4939-3197-2_3
发表时间：
2016-01-01
期刊：
NUCLEIC ACID APTAMERS
影响因子：
--
作者：
Catuogno, Silvia;Esposito, Carla Lucia;de Franciscis, Vittorio
通讯作者：
de Franciscis, Vittorio