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Science. 2011 Sep 2;333(6047):1307-11. doi: 10.1126/science.1205527.

Multi-input RNAi-based logic circuit for identification of specific cancer cells.

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Faculty of Arts and Sciences (FAS) Center for Systems Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.


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.

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