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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,
Yaakov Benenson1,3,,
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.
Present address: Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, Basel 4058, Switzerland.
To whom correspondence should be addressed. E-mail: kobi.benenson{at}bsse.ethz.ch (Y.B.); rweiss{at}mit.edu (R.W.)
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In Science Signaling
EDITORS' CHOICE
Valda Vinson (6 September 2011) Sci. Signal.4 (189), ec246.
[DOI: 10.1126/scisignal.4189ec246] |Abstract »
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|Abstract »|Full Text »|PDF »
Yaakov Benenson1,3,
Present address: Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, Basel 4058, Switzerland.
To whom correspondence should be addressed. E-mail: 
