Letter abstract
Nature Biotechnology 25, 795 - 801 (2007)
Published online: 21 May 2007 | doi:10.1038/nbt1307
A universal RNAi-based logic evaluator that operates in mammalian cells
Keller Rinaudo1,4, Leonidas Bleris1,4, Rohan Maddamsetti1, Sairam Subramanian2,3, Ron Weiss2,3 & Yaakov Benenson1
Abstract
Molecular automata1, 2, 3 that combine sensing4, 5, 6, computation7, 8, 9, 10, 11, 12 and actuation13, 14 enable programmable manipulation of biological systems. We use RNA interference (RNAi)15 in human kidney cells to construct a molecular computing core that implements general Boolean logic1, 3, 8, 9, 10, 11, 12, 16 to make decisions based on endogenous molecular inputs. The state of an endogenous input is encoded by the presence or absence of 'mediator' small interfering RNAs (siRNAs). The encoding rules, combined with a specific arrangement of the siRNA targets in a synthetic gene network17, allow direct evaluation of any Boolean expression in standard forms using siRNAs and indirect evaluation using endogenous inputs. We demonstrate direct evaluation of expressions with up to five logic variables. Implementation of the encoding rules through sensory up- and down-regulatory links between the inputs and siRNA mediators will allow arbitrary Boolean decision-making using these inputs.
- FAS Center for Systems Biology, Harvard University, 7 Divinity Ave., Cambridge, Massachusetts 02138 USA.
- Department of Electrical Engineering, Princeton University, E-Quad B-312, Olden St., Princeton, New Jersey 08544, USA.
- Department of Molecular Biology, Princeton University, E-Quad B-312, Olden St., Princeton, New Jersey 08544, USA.
- These authors contributed equally to this work.
Correspondence to: Yaakov Benenson1 e-mail: kbenenson@cgr.harvard.edu
Correspondence to: Ron Weiss2,3 e-mail: rweiss@princeton.edu
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