Efforts to construct synthetic networks in living cells have been hindered by the limited number of regulatory components that provide wide dynamic range and low crosstalk. Here, we report a class of de-novo-designed prokaryotic riboregulators called toehold switches that activate gene expression in response to cognate RNAs with arbitrary sequences. Toehold switches provide a high level of orthogonality and can be forward engineered to provide average dynamic range above 400. We show that switches can be integrated into the genome to regulate endogenous genes and use them as sensors that respond to endogenous RNAs. We exploit the orthogonality of toehold switches to regulate 12 genes independently and to construct a genetic circuit that evaluates 4-input AND logic. Toehold switches, with their wide dynamic range, orthogonality, and programmability, represent a versatile and powerful platform for regulation of translation, offering diverse applications in molecular biology, synthetic biology, and biotechnology.
Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements
De novo automated design of small RNA circuits for engineering synthetic riboregulation in living cells
An adaptor from translational to transcriptional control enables predictable assembly of complex regulation
Molecular Titration Promotes Oscillations and Bistability in Minimal Network Models with Monomeric Regulators
A Panel of Protease-Responsive RNA Polymerases Respond to Biochemical Signals by Production of Defined RNA Outputs in Live Cells
Improving fold activation of small transcription activating RNAs (STARs) with rational RNA engineering strategies
Exploring the Dynamics and Mutational Landscape of Riboregulation with a Minimal Synthetic Circuit in Living Cells
A cis-encoded sRNA, Hfq and mRNA secondary structure act independently to suppress IS200 transposition
Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells
Rapid Detection Strategies for the Global Threat of Zika Virus: Current State, New Hypotheses, and Limitations
Highly efficient in vitro and in vivo delivery of functional RNAs using new versatile MS2-chimeric retrovirus-like particles
Achieving large dynamic range control of gene expression with a compact RNA transcription-translation regulator
Spatio-Temporal Gene Induction Systems in the Heterocyst-Forming Multicellular Cyanobacterium Anabaena sp. PCC 7120
Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation
Applying a riboregulator as a new chromosomal gene regulation tool for higher glycogen production in Synechocystis sp. PCC 6803
Emerging Microtechnologies and Automated Systems for Rapid Bacterial Identification and Antibiotic Susceptibility Testing
Re-direction of carbon flux to key precursor malonyl-CoA via artificial small RNAs in photosynthetic Synechocystis sp. PCC 6803
Diversity, versatility and complexity of bacterial gene regulation mechanisms: opportunities and drawbacks for applications in synthetic biology
Next-level riboswitch development-implementation of Capture-SELEX facilitates identification of a new synthetic riboswitch
A modular clamp-like mechanism to regulate the activity of nucleic-acid target-responsive nanoswitches with external activators
Homogeneous and universal transduction of various nucleic acids to an off-shelf device based on programmable toehold switch sensing
Extremely Low Leakage Expression Systems Using Dual Transcriptional-Translational Control for Toxic Protein Production
Rapid bacterial detection and antibiotic susceptibility testing in whole blood using one-step, high throughput blood digital PCR.
Homogeneous and Universal Detection of Various Targets with a Dual-Step Transduced Toehold Switch Sensor.
Allosteric DNA nanoswitches for controlled release of a molecular cargo triggered by biological inputs
Novel nucleic acid detection strategies based on CRISPR-Cas systems: From construction to application
Nanopore Targeted Sequencing for the Accurate and Comprehensive Detection of SARS-CoV-2 and Other Respiratory Viruses
Fine and bidirectional regulation of toehold-mediated DNA strand displacement by a wedge-like DNA tool.
Chemical Translational Biology-Guided Molecular Diagnostics: The Front Line To Mediate the Current SARS-CoV-2 Pandemic
Innovative technologies for point-of-care testing of viral hepatitis in low-resource and decentralized settings
The importance of thermodynamics for molecular systems, and the importance of molecular systems for thermodynamics
Low-cost detection of norovirus using paper-based cell-free systems and synbody-based viral enrichment
Using in-cell SHAPE-Seq and simulations to probe structure-function design principles of RNA transcriptional regulators
Computational design of small transcription activating RNAs for versatile and dynamic gene regulation
Advances in engineered trans-acting regulatory RNAs and their application in bacterial genome engineering
Engineering metabolite-responsive transcriptional factors to sense small molecules in eukaryotes: current state and perspectives
Synthetic biology in various cellular and molecular fields: applications, limitations, and perspective.
Rapid generation of sequence-diverse terminator libraries and their parameterization using quantitative Term-Seq
Determining the folding and binding free energy of DNA-based nanodevices and nanoswitches using urea titration curves
Flexible regulation of DNA displacement reaction through nucleic acid-recognition enzyme and its application in keypad lock system and biosensing
High-throughput in vivo mapping of RNA accessible interfaces to identify functional sRNA binding sites
Evolution of C-Terminal Modification Tolerance in Full-Length and Split T7 RNA Polymerase Biosensors
Developments of Riboswitches and Toehold Switches for Molecular Detection-Biosensing and Molecular Diagnostics.
Conditional guide RNA through two intermediate hairpins for programmable CRISPR/Cas9 function: building regulatory connections between endogenous RNA expressions.
A simple and low-cost paper-based colorimetric method for detecting and distinguishing the GII.4 and GII.17 genotypes of norovirus.
Endogenous promoter-driven sgRNA for monitoring the expression of low-abundance transcripts and lncRNAs.
Challenges and opportunities with CRISPR activation in bacteria for data-driven metabolic engineering.
Signal amplification and optimization of riboswitch-based hybrid inputs by modular and titratable toehold switches.
Design and Construction of Generalizable RNA-Protein Hybrid Controllers by Level-Matched Genetic Signal Amplification
Rational engineering of a modular bacterial CRISPR-Cas activation platform with expanded target range.
Recent advances in tuning the expression and regulation of genes for constructing microbial cell factories.
Data-Driven and in Silico-Assisted Design of Broad Host-Range Minimal Intrinsic Terminators Adapted for Bacteria.
Nonequilibrium thermodynamics of the RNA-RNA interaction underlying a genetic transposition program.
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