ArticleMolecular systems biology2016
Model-guided combinatorial optimization of complex synthetic gene networks.
Article in Molecular systems biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Predictive genetic circuit design for phenotype reprogramming in plants.Nature communications · 2025Article
- Synthetic gene circuits for cell state detection and protein tuning in human pluripotent stem cells.Molecular systems biology · 2022Article
- A synthetic circuit for buffering gene dosage variation between individual mammalian cells.Nature communications · 2021Article
- Precise determination of input-output mapping for multimodal gene circuits using data from transient transfection.PLoS computational biology · 2020Article
- Artificial signaling in mammalian cells enabled by prokaryotic two-component system.Nature chemical biology · 2020Article
- Engineering advanced cancer therapies with synthetic biology.Nature reviews. Cancer · 2019Review
- A frame-shifted gene, which rescued its function by non-natural start codons and its application in constructing synthetic gene circuits.Journal of biological engineering · 2019Article
- Synthetic RNA-based logic computation in mammalian cells.Nature communications · 2018Article
- Genetic programs can be compressed and autonomously decompressed in live cells.Nature nanotechnology · 2018Article
- Article
- Mapping the operational landscape of microRNAs in synthetic gene circuits.NPJ systems biology and applications · 2018Article
- Multiplexing Engineered Receptors for Multiparametric Evaluation of Environmental Ligands.ACS synthetic biology · 2017Article
- Synthetic Gene Expression Circuits for Designing Precision Tools in Oncology.Frontiers in cell and developmental biology · 2017Review
- Model-guided combinatorial optimization of complex synthetic gene networks.Molecular systems biology · 2016Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Constructing gene circuits that satisfy quantitative performance criteria has been a long-standing challenge in synthetic biology. Here, we show a strategy for optimizing a complex three-gene circuit, a novel proportional miRNA biosensor, using predictive modeling to initiate a search in the phase space of sensor genetic composition. We generate a library of sensor circuits using diverse genetic building blocks in order to access favorable parameter combinations and uncover specific genetic compositions with greatly improved dynamic range. The combination of high-throughput screening data and the data obtained from detailed mechanistic interrogation of a small number of sensors was used to validate the model. The validated model facilitated further experimentation, including biosensor reprogramming and biosensor integration into larger networks, enabling in principle arbitrary logic with miRNA inputs using normal form circuits. The study reveals how model-guided generation of genetic diversity followed by screening and model validation can be successfully applied to optimize performance of complex gene networks without extensive prior knowledge.
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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.