The ability to engineer synthetic systems in the biochemical context is constantly being improved and has a profound societal impact. Linear system design is one of the most pervasive methods applied in control tasks, and its biochemical realization has been proposed by Oishi and Klavins and advanced further in recent years. However, several technical issues remain unsolved. Specifically, the design process is not fully automated from specification at the transfer function level, systems once designed often lack dynamic adaptivity to environmental changes, matching rate constants of reactions is not always possible, and implementation may be approximative and greatly deviate from the specifications. Building upon the work of Oishi and Klavins, this paper overcomes these issues by introducing a design flow that transforms a transfer-function specification of a linear system into a set of chemical reactions, whose input-output response precisely conforms to the specification. This system is implementable using the DNA strand displacement technique. The underlying configurability is embedded into primitive components and template modules, and thus the entire system is adaptive. Simulation of DNA strand displacement implementation confirmed the feasibility and superiority of the proposed synthesis flow.
A synthetic approach to biology is a promising technique for various applications. Recent advancements have demonstrated the feasibility of constructing synthetic two-input logic gates in Escherichia coli cells with long-term memory based on DNA inversion induced by recombinases. Moreover, recent evidences indicate that DNA inversion mediated by genome editing tools is possible. Powerful genome editing technologies, such as CRISPR-Cas9 systems, have great potential to be exploited to implement large-scale recombinase-based circuits. What remains unclear is how to construct arbitrary Boolean functions based on these emerging technologies. In this paper, we lay the theoretical foundation formalizing the connection between recombinase-based genetic circuits and Boolean functions. It enables systematic construction of any given Boolean function using recombinase-based logic gates. We further develop a methodology leveraging existing electronic design automation (EDA) tools to automate the synthesis of complex recombinase-based genetic circuits with respect to area and delay optimization. In silico experimental results demonstrate the applicability of our proposed methods as a useful tool for recombinase-based genetic circuit synthesis and optimization.
A synthetic approach to biology is a promising technique for various applications. Recent advancements have demonstrated the feasibility of constructing synthetic two-input logic gates in Escherichia coli cells with long-term memory based on DNA inversion induced by recombinases. Moreover, recent evidences indicate that DNA inversion mediated by genome editing tools is possible. Powerful genome editing technologies, such as CRISPR-Cas9 systems, have great potential to be exploited to implement largescale recombinase-based circuits. What remains unclear is how to construct arbitrary Boolean functions based on these emerging technologies. In this paper, we lay the theoretical foundation formalizing the connection between recombinase-based genetic circuits and Boolean functions. It enables systematic construction of any given Boolean function using recombinase-based logic gates. We further develop a methodology leveraging existing electronic design automation (EDA) tools to automate the synthesis of complex recombinase-based genetic circuits with respect to area and delay optimization. In silico experimental results demonstrate the applicability of our proposed methods as a useful tool for recombinase-based genetic circuit synthesis and optimization.The development of synthetic biology shows the feasibility to implement computing devices with DNA genetic circuits in living cells. Synthetic cellular designs often intended to implement certain functions that make cells respond to specific environmental stimuli or even change their growth and cellular development. For instance, synthetic toggle switches 1 and genetic oscillators 2-5 can be used to control cell metabolism, synthetic counters 6 can be potentially applied to the regulation of telomere length and cell aggregation, and genetic logic gates [7][8][9][10] can achieve digital computation in response to stimulus input signals. In addition to these transcription-based DNA circuits, new emerging translational mRNA circuits 11 are likely to have impact on mammalian regenerative medicine and gene therapy. Through the genetic engineering, synthetic cellular circuits are potentially useful to perform therapeutic and diagnostic functions.For some situations where noxious chemical stimuli exist for many cell generations, the computational results from the synthetic circuits in parent cells are required to be propagated to their daughter cells so that the daughter cells can save time to respond to the environmental stimuli. To achieve this transgenerational memory, one possible method is to store the computational results in separate synthetic memory devices which can be duplicated in cell divisions. In the recent work of Siuti et al.12 , a more efficient scheme for constructing synthetic cellular circuits with integrated logic and memory was proposed, where the computational result was automatically stored in the computing circuit configuration and the changes of configuration can be propagated to its descendant cells. The so-implemented circuits were built based on re...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.