Integrated nanosensors to determine levels and functional activity of human telomerase
Integrated nanosensors to determine levels and functional activity of human telomerase
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DOI：
10.1593/neo.08350
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发表时间：
2008-10-01
期刊：
影响因子：
4.8
通讯作者：
Weissleder, Ralph
中科院分区：
文献类型：
--
作者：
Perez, J. Manuel;Grimm, Jan;Weissleder, Ralph
端粒酶是一种重要的致癌酶，目前正在开发一些新的端粒酶抑制剂。由于抑制可以在蛋白质或酶活性水平上实现，因此对这些参数的独立测量对于开发有效的治疗剂非常重要。在目前的研究中，我们开发了一套功能性磁性纳米传感器，能够测量端粒酶的浓度，以及它的酶活性。该方法基于磁松弛开关试验，可在粗组织样品中进行，速度快，灵敏度高。使用这种方法，我们能够在各种癌症和正常细胞系中检测不同数量的端粒酶蛋白和活性。此外，我们能够研究磷酸化对端粒酶活性的影响。该系统不仅可以为抗端粒酶治疗提供一种快速的评价方法，还可以应用于其他癌症标志物的研究。
Telomerase is a key oncogenic enzyme, and a number of novel telomerase inhibitors are currently under development. Because inhibition can be achieved either at the protein or at the enzymatic activity level, independent measurements of these parameters are important in the development of effective therapeutic agents. In the current study, we have developed a set of functional magnetic nanosensors capable of measuring the concentration of telomerase, as well as its enzymatic activity in parallel. The method is based on a magnetic relaxation switch assay, which can be performed in crude tissue samples and is fast and extremely sensitive. Using this method, we were able to detect different amounts of telomerase protein and activity in various cancer and normal cell lines. Furthermore, we were able to study the effect of phosphorylation on telomerase activity. This system not only could provide a rapid assay for the evaluation of antitelomerase therapies but could also be implemented to the study of other cancer markers.