Dataset Information

Types I and V Anti-CRISPR Proteins: From Phage Defense to Eukaryotic Synthetic Gene Circuits.

ABSTRACT: Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins), a prokaryotic RNA-mediated adaptive immune system, has been repurposed for gene editing and synthetic gene circuit construction both in bacterial and eukaryotic cells. In the last years, the emergence of the anti-CRISPR proteins (Acrs), which are natural OFF-switches for CRISPR-Cas, has provided a new means to control CRISPR-Cas activity and promoted a further development of CRISPR-Cas-based biotechnological toolkits. In this review, we focus on type I and type V-A anti-CRISPR proteins. We first narrate Acrs discovery and analyze their inhibitory mechanisms from a structural perspective. Then, we describe their applications in gene editing and transcription regulation. Finally, we discuss the potential future usage-and corresponding possible challenges-of these two kinds of anti-CRISPR proteins in eukaryotic synthetic gene circuits.

SUBMITTER: Yu L

PROVIDER: S-EPMC7556299 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Types I and V Anti-CRISPR Proteins: From Phage Defense to Eukaryotic Synthetic Gene Circuits.

Yu Lifang L Marchisio Mario Andrea MA

Frontiers in bioengineering and biotechnology 20200930

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins), a prokaryotic RNA-mediated adaptive immune system, has been repurposed for gene editing and synthetic gene circuit construction both in bacterial and eukaryotic cells. In the last years, the emergence of the anti-CRISPR proteins (Acrs), which are natural OFF-switches for CRISPR-Cas, has provided a new means to control CRISPR-Cas activity and promoted a further development of CRISPR-Cas-based biot ...[more]

PMID: 33102460

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Project description:BackgroundThe modular design of synthetic gene circuits via composable parts (DNA segments) and pools of signal carriers (molecules such as RNA polymerases and ribosomes) has been successfully applied to bacterial systems. However, eukaryotic cells are becoming a preferential host for new synthetic biology applications. Therefore, an accurate description of the intricate network of reactions that take place inside eukaryotic parts and pools is necessary. Rule-based modeling approaches are increasingly used to obtain compact representations of reaction networks in biological systems. However, this approach is intrinsically non-modular and not suitable per se for the description of composable genetic modules. In contrast, the Model Description Language (MDL) adopted by the modeling tool ProMoT is highly modular and it enables a faithful representation of biological parts and pools.ResultsWe developed a computational framework for the design of complex (eukaryotic) gene circuits by generating dynamic models of parts and pools via the joint usage of the BioNetGen rule-based modeling approach and MDL. The framework converts the specification of a part (or pool) structure into rules that serve as inputs for BioNetGen to calculate the part's species and reactions. The BioNetGen output is translated into an MDL file that gives a complete description of all the reactions that take place inside the part (or pool) together with a proper interface to connect it to other modules in the circuit. In proof-of-principle applications to eukaryotic Boolean circuits with more than ten genes and more than one thousand reactions, our framework yielded proper representations of the circuits' truth tables.ConclusionsFor the model-based design of increasingly complex gene circuits, it is critical to achieve exact and systematic representations of the biological processes with minimal effort. Our computational framework provides such a detailed and intuitive way to design new and complex synthetic gene circuits.

Dataset Information

Types I and V Anti-CRISPR Proteins: From Phage Defense to Eukaryotic Synthetic Gene Circuits.

Publications

Types I and V Anti-CRISPR Proteins: From Phage Defense to Eukaryotic Synthetic Gene Circuits.

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