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Constructing Controllable Logic Circuits Based on DNAzyme Activity.

ABSTRACT: Recently, DNA molecules have been widely used to construct advanced logic devices due to their unique properties, such as a simple structure and predictable behavior. In fact, there are still many challenges in the process of building logic circuits. Among them, the scalability of the logic circuit and the elimination of the crosstalk of the cascade circuit have become the focus of research. Inspired by biological allosteric regulation, we developed a controllable molecular logic circuit strategy based on the activity of DNAzyme. The E6 DNAzyme sequence was temporarily blocked by hairpin DNA and activated under appropriate input trigger conditions. Using a substrate with ribonucleobase (rA) modification as the detection strand, a series of binary basic logic gates (YES, AND, and INHIBIT) were implemented on the computational component platform. At the same time, we demonstrate a parallel demultiplexer and two multi-level cascade circuits (YES-YES and YES-Three input AND (YES-TAND)). In addition, the leakage of the cascade process was reduced by exploring factors such as concentration and DNA structure. The proposed DNAzyme activity regulation strategy provides great potential for the expansion of logic circuits in the future.

SUBMITTER: Yang F

PROVIDER: S-EPMC6891523 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Constructing Controllable Logic Circuits Based on DNAzyme Activity.

Yang Fengjie F Liu Yuan Y Wang Bin B Zhou Changjun C Zhang Qiang Q

Molecules (Basel, Switzerland) 20191115 22

Recently, DNA molecules have been widely used to construct advanced logic devices due to their unique properties, such as a simple structure and predictable behavior. In fact, there are still many challenges in the process of building logic circuits. Among them, the scalability of the logic circuit and the elimination of the crosstalk of the cascade circuit have become the focus of research. Inspired by biological allosteric regulation, we developed a controllable molecular logic circuit strateg ...[more]

PMID: 31731630

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Project description:BACKGROUND:In silico experiments, with the aid of computer simulation, speed up the process of in vitro or in vivo experiments. Cancer therapy design is often based on signalling pathway. MicroRNAs (miRNA) are small non-coding RNA molecules. In several kinds of diseases, including cancer, hepatitis and cardiovascular diseases, they are often deregulated, acting as oncogenes or tumor suppressors. miRNA therapeutics is based on two main kinds of molecules injection: miRNA mimics, which consists of injection of molecules that mimic the targeted miRNA, and antagomiR, which consists of injection of molecules inhibiting the targeted miRNA. Nowadays, the research is focused on miRNA therapeutics. This paper addresses cancer related signalling pathways to investigate miRNA therapeutics. RESULTS:In order to prove our approach, we present two different case studies: non-small cell lung cancer and melanoma. KEGG signalling pathways are modelled by a digital circuit. A logic value of 1 is linked to the expression of the corresponding gene. A logic value of 0 is linked to the absence (not expressed) gene. All possible relationships provided by a signalling pathway are modelled by logic gates. Mutations, derived according to the literature, are introduced and modelled as well. The modelling approach and analysis are widely discussed within the paper. MiRNA therapeutics is investigated by the digital circuit analysis. The most effective miRNA and combination of miRNAs, in terms of reduction of pathogenic conditions, are obtained. A discussion of obtained results in comparison with literature data is provided. Results are confirmed by existing data. CONCLUSIONS:The proposed study is based on drug discovery and miRNA therapeutics and uses a digital circuit simulation of a cancer pathway. Using this simulation, the most effective combination of drugs and miRNAs for mutated cancer therapy design are obtained and these results were validated by the literature. The proposed modelling and analysis approach can be applied to each human disease, starting from the corresponding signalling pathway.

Dataset Information

Constructing Controllable Logic Circuits Based on DNAzyme Activity.

Publications

Constructing Controllable Logic Circuits Based on DNAzyme Activity.

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