Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells
Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells
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DOI：
10.1126/science.1205527
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发表时间：
2011-09-02
期刊：
影响因子：
56.9
通讯作者：
Benenson, Yaakov
中科院分区：
文献类型：
--
作者：
Xie, Zhen;Wroblewska, Liliana;Benenson, Yaakov
工程生物系统集成了多输入传感、复杂的信息处理和在活细胞中精确调节的驱动，可能在各种应用中有用。例如，抗癌疗法可以被设计成检测并对单个细胞中复杂的细胞状况做出高度特异性的反应。在这里，我们展示了一个可扩展的转录/转录后合成调节电路--一个细胞型的“分类器”--它感知一组可定制的内源microRNA的表达水平，并只有在表达水平与预定的感兴趣的图谱匹配时才触发细胞反应。我们证明，HeLa癌细胞分类器选择性地识别HeLa细胞并触发凋亡，而不影响非HeLa细胞类型。该方法还提供了对其他复杂单元状态的程序化响应的通用平台。
Engineered biological systems that integrate multi-input sensing, sophisticated information processing, and precisely regulated actuation in living cells could be useful in a variety of applications. For example, anticancer therapies could be engineered to detect and respond to complex cellular conditions in individual cells with high specificity. Here, we show a scalable transcriptional/posttranscriptional synthetic regulatory circuit-a cell-type "classifier"-that senses expression levels of a customizable set of endogenous microRNAs and triggers a cellular response only if the expression levels match a predetermined profile of interest. We demonstrate that a HeLa cancer cell classifier selectively identifies HeLa cells and triggers apoptosis without affecting non-HeLa cell types. This approach also provides a general platform for programmed responses to other complex cell states.