ArticleProceedings of the National Academy of Sciences of the United States of America2012
De novo automated design of small RNA circuits for engineering synthetic riboregulation in living cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed.
- Small Regulatory RNAs in Prokaryotes: Key Features, Identification, Environmental Roles, and Applications.Microorganisms · 2026Review
- SUPER: Upcycling Genetic Parts for Precise Gene Expression Control, Leakage Minimization, and Genetic Circuit Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- In Silico Design of Interacting RNA Sequences Using the MODENA Web Server.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Digitizing the Blue Light-Activated T7 RNA Polymerase System with aACS synthetic biology · 2025Article
- Optimization of a High-Throughput Screen for Monitoring Disease-Associated Protein Misfolding and Aggregation in Bacteria.ACS synthetic biology · 2025Article
- Intelligent guide RNA: dual toehold switches for modulating luciferase in the presence of trigger RNA.Communications biology · 2024Article
- START: A Versatile Platform for Bacterial Ligand Sensing with Programmable Performances.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Simultaneous enhancement of multiple functional properties using evolution-informed protein design.Nature communications · 2024Article
- Regulatory RNAs inSynthetic and systems biotechnology · 2024Review
- T7 phage-assisted evolution of riboswitches using error-prone replication and dual selection.Scientific reports · 2024Article
- Design of artificial small regulatorySynthetic and systems biotechnology · 2023Article
- Hydrogel on a Smart Nanomaterial Interface to Carry Therapeutics for Digitalized Glioma Treatment.Gels (Basel, Switzerland) · 2022Review
- Model-Based Investigation of the Relationship between Regulation Level and Pulse Property of I1-FFL Gene Circuits.ACS synthetic biology · 2022Article
- Rational design of hairpin RNA excited states reveals multi-step transitions.Nature communications · 2022Article
- Design and Evaluation of Synthetic RNA-Based Incoherent Feed-Forward Loop Circuits.Biomolecules · 2021Article
- Review
- A Web Server for Designing Molecular Switches Composed of Two Interacting RNAs.International journal of molecular sciences · 2021Article
- Conditional guide RNA through two intermediate hairpins for programmable CRISPR/Cas9 function: building regulatory connections between endogenous RNA expressions.Nucleic acids research · 2020Article
- Sequence-to-function deep learning frameworks for engineered riboregulators.Nature communications · 2020Article
- Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A grand challenge in synthetic biology is to use our current knowledge of RNA science to perform the automatic engineering of completely synthetic sequences encoding functional RNAs in living cells. We report here a fully automated design methodology and experimental validation of synthetic RNA interaction circuits working in a cellular environment. The computational algorithm, based on a physicochemical model, produces novel RNA sequences by exploring the space of possible sequences compatible with predefined structures. We tested our methodology in Escherichia coli by designing several positive riboregulators with diverse structures and interaction models, suggesting that only the energy of formation and the activation energy (free energy barrier to overcome for initiating the hybridization reaction) are sufficient criteria to engineer RNA interaction and regulation in bacteria. The designed sequences exhibit nonsignificant similarity to any known noncoding RNA sequence. Our riboregulatory devices work independently and in combination with transcription regulation to create complex logic circuits. Our results demonstrate that a computational methodology based on first-principles can be used to engineer interacting RNAs with allosteric behavior in living cells.
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