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  • Title: Develop reusable and combinable designs for transcriptional logic gates.
    Author: Zhan J, Ding B, Ma R, Ma X, Su X, Zhao Y, Liu Z, Wu J, Liu H.
    Journal: Mol Syst Biol; 2010 Jul 13; 6():388. PubMed ID: 20631682.
    Abstract:
    One limit on developing complex synthetic gene circuits is the lack of basic components such as transcriptional logic gates that can process combinatorial inputs. Here, we propose a strategy to construct such components based on reusable designs and convergent reengineering of well-studied natural systems. We demonstrated the strategy using variants of the transcription factor (TF) LacI and operator Olac that form specifically interacting pairs. Guided by a mathematical model derived from existing quantitative knowledge, rational designs of transcriptional NAND, NOR and NOT gates have been realized. The NAND gates have been designed based on direct protein-protein interactions in coupling with DNA looping. We demonstrated that the designs are reusable: a multiplex of logic devices can be readily created using the same designs but different combinations of sequence variants. The designed logic gates are combinable to form compound circuits: a demonstration logic circuit containing all three types of designed logic gates has been synthesized, and the circuit truthfully reproduces the pre-designed input-output logic relations.
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