ArticleNature chemical biology2014
Digital switching in a biosensor circuit via programmable timing of gene availability.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Synthetic gene circuits in plants: recent advances and challenges.Quantitative plant biology · 2025Review
- Engineering intelligent chassis cells via recombinase-based MEMORY circuits.Nature communications · 2024Article
- Engineering and application of LacI mutants with stringent expressions.Microbial biotechnology · 2024Article
- Orthogonal LoxPsym sites allow multiplexed site-specific recombination in prokaryotic and eukaryotic hosts.Nature communications · 2024Article
- Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast.Nature communications · 2024Article
- Next generation synthetic memory via intercepting recombinase function.Nature communications · 2023Article
- Molecular recording: transcriptional data collection into the genome.Current opinion in biotechnology · 2023Review
- Synthetic gene circuits for cell state detection and protein tuning in human pluripotent stem cells.Molecular systems biology · 2022Article
- Pairing of single mutations yields obligate Cre-type site-specific recombinases.Nucleic acids research · 2022Article
- Precise determination of input-output mapping for multimodal gene circuits using data from transient transfection.PLoS computational biology · 2020Article
- Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapy.Nature communications · 2019Article
- Encryption and steganography of synthetic gene circuits.Nature communications · 2018Article
- Synthetic RNA-based logic computation in mammalian cells.Nature communications · 2018Article
- Synthetic control systems for high performance gene expression in mammalian cells.Nucleic acids research · 2018Article
- Designing cell function: assembly of synthetic gene circuits for cell biology applications.Nature reviews. Molecular cell biology · 2018Review
- Genetic programs can be compressed and autonomously decompressed in live cells.Nature nanotechnology · 2018Article
- Programming gene and engineered-cell therapies with synthetic biology.Science (New York, N.Y.) · 2018Review
- Digital logic circuits in yeast with CRISPR-dCas9 NOR gates.Nature communications · 2017Article
- Achieving large dynamic range control of gene expression with a compact RNA transcription-translation regulator.Nucleic acids research · 2017Article
- Designed cell consortia as fragrance-programmable analog-to-digital converters.Nature chemical biology · 2017Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Transient delivery of gene circuits is required in many potential applications of synthetic biology, yet the pre-steady-state processes that dominate this delivery route pose major challenges for robust circuit deployment. Here we show that site-specific recombinases can rectify undesired effects by programmable timing of gene availability in multigene circuits. We exemplify the concept with a proportional sensor for endogenous microRNA (miRNA) and show a marked reduction in its ground state leakage due to desynchronization of the circuit's repressor components and their repression target. The new sensors display a dynamic range of up to 1,000-fold compared to 20-fold in the standard configuration. We applied the approach to classify cell types on the basis of miRNA expression profile and measured >200-fold output differential between positively and negatively identified cells. We also showed major improvements in specificity with cytotoxic output. Our study opens new venues in gene circuit design via judicious temporal control of circuits' genetic makeup.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.