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Science 333 (6047): 1307-1311

Copyright © 2011 by the American Association for the Advancement of Science

Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells

Zhen Xie,1,2,* Liliana Wroblewska,2 Laura Prochazka,3 Ron Weiss,2,4,{dagger} Yaakov Benenson1,3,{dagger},{ddagger}

Abstract: 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.

1 Faculty of Arts and Sciences (FAS) Center for Systems Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
2 Department of Biological Engineering, Massachusetts Institute of Technology (MIT), 40 Ames Street, Cambridge, MA 02142, USA.
3 Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, Mattenstrasse 26, Basel 4058, Switzerland.
4 Department of Electrical Engineering and Computer Science, MIT, 40 Ames Street, Cambridge MA 02142, USA.

* Present address: Department of Biological Engineering, MIT, 40 Ames Street, Cambridge, MA 02142, USA.

{ddagger} Present address: Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, Basel 4058, Switzerland.

{dagger} To whom correspondence should be addressed. E-mail: kobi.benenson{at} (Y.B.); rweiss{at} (R.W.)

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