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Abstract DNA devices have been shown to be capable of evaluating Boolean logic. Several robust designs for DNA circuits have been demonstrated. Some prior DNA‐based circuits are use‐once circuits since the gate motifs of the DNA circuits get permanently destroyed as a side effect of the computation, and hence cannot respond correctly to subsequent changes in inputs. Other DNA‐based circuits use a large reservoir of buffered gates to replace the working gates of the circuit and can be used to drive a finite number of computation cycles. In many applications of DNA circuits, the inputs are inherently asynchronous, and this necessitates that the DNA circuits be asynchronous: the output must always be correct regardless of differences in the arrival time of inputs. This paper demonstrates: 1) renewable DNA circuits, which can be manually reverted to their original state by addition of DNA strands, and 2) time‐responsive DNA circuits, where if the inputs change over time, the DNA circuit can recompute the output correctly based on the new inputs, that are manually added after the system has been reset. The properties of renewable, asynchronous, and time‐responsiveness appear to be central to molecular‐scale systems; for example, self‐regulation in cellular organisms.
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Distributed Implementation of Boolean Functions by Transcriptional Synthetic Circuits
Starting in the early 2000s, sophisticated technologies have been developed for the rational construction of synthetic genetic networks that implement specified logical functionalities. Despite impressive progress, however, the scaling necessary in order to achieve greater computational power has been hampered by many constraints, including repressor toxicity and the lack of large sets of mutually orthogonal repressors. As a consequence, a typical circuit contains no more than roughly seven repressor-based gates per cell. A possible way around this scalability problem is to distribute the computation among multiple cell types, each of which implements a small subcircuit, which communicate among themselves using diffusible small molecules (DSMs). Examples of DSMs are those employed by quorum sensing systems in bacteria. This paper focuses on systematic ways to implement this distributed approach, in the context of the evaluation of arbitrary Boolean functions. The unique characteristics of genetic circuits and the properties of DSMs require the development of new Boolean synthesis methods, distinct from those classically used in electronic circuit design. In this work, we propose a fast algorithm to synthesize distributed realizations for any Boolean function, under constraints on the number of gates per cell and the number of orthogonal DSMs. The method is based on an exact synthesis algorithm to find the minimal circuit per cell, which in turn allows us to build an extensive database of Boolean functions up to a given number of inputs. For concreteness, we will specifically focus on circuits of up to 4 inputs, which might represent, for example, two chemical inducers and two light inputs at different frequencies. Our method shows that, with a constraint of no more than seven gates per cell, the use of a single DSM increases the total number of realizable circuits by at least 7.58-fold compared to centralized computation. Moreover, when allowing two DSM’s, one can realize 99.995% of all possible 4-input Boolean functions, still with at most 7 gates per cell. The methodology introduced here can be readily adapted to complement recent genetic circuit design automation software. A toolbox that uses the proposed algorithm was created and made available at https://github. com/sontaglab/DBC/.
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- Award ID(s):
- 1849588
- PAR ID:
- 10175714
- Date Published:
- Journal Name:
- ACS Synthetic Biology
- ISSN:
- 2161-5063
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acssynbio.0c00228
