ArticleNature biotechnology2017
Large-scale design of robust genetic circuits with multiple inputs and outputs for mammalian cells.
Article in Nature biotechnology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed.
- Large serine recombinase-mediated gene insertion for high-throughput screens: advantages, design principles, and applications.Nucleic acids research · 2026Review
- Programmable promoter editing for precise control of transgene expression.Nature biotechnology · 2026Article
- Plant Cell-on-Chip (PCOC): Exploring the Electrical Modulation Capability of Plant Cells.Micromachines · 2026Article
- Designing and testing CRISPRi-based synthetic gene circuits in plants.Nature protocols · 2026Review
- Modular Scalable Synthetic Gene Circuits for Complex Functions Within Minimal Computational Layers in Human Cells.Nature communications · 2026Article
- Synthetic circuits for cell ratio control.Nature · 2026Article
- Protecting cells at the genetic level and simulating unauthorized access via a biohackathon.Science advances · 2026Article
- Continuously tunable multistability in DNA replication networks.Nature communications · 2026Article
- From Negative Feedback to Integrated Control: Recombinase-Based Strategies for Mitigating Resource Competition.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Probing direct interactions between nuclear proteins in cells with nxReLo.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording.Nature biotechnology · 2025Article
- Cell-free recombinase-integrated Boolean output system.Cell systems · 2025Article
- Molecular insights into the Drosophila piRNA pathway via systematic ReLo protein interaction screening and structure prediction.Nucleic acids research · 2025Article
- Synthetic protein degradation circuits using programmable cleavage and ligation by Sortase A.Nature communications · 2025Article
- MitoScribe single-cell molecular recorder logs graded signaling dynamics into mitochondrial DNA.bioRxiv : the preprint server for biology · 2025Article
- Multiplexing light-inducible recombinases to control cell fate, Boolean logic, and cell patterning in mammalian cells.Science advances · 2025Article
- Valproic acid-induced teratogenicity is driven by senescence and prevented by Rapamycin in human spinal cord and animal models.Molecular psychiatry · 2025Article
- The switch-liker's guide to plant synthetic gene circuits.The Plant journal : for cell and molecular biology · 2025Review
- Creation of a eukaryotic multiplexed site-specific inversion system and its application for metabolic engineering.Nature communications · 2025Article
- Synthetic gene circuits in plants: recent advances and challenges.Quantitative plant biology · 2025Review
73 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
Engineered genetic circuits for mammalian cells often require extensive fine-tuning to perform as intended. We present a robust, general, scalable system, called 'Boolean logic and arithmetic through DNA excision' (BLADE), to engineer genetic circuits with multiple inputs and outputs in mammalian cells with minimal optimization. The reliability of BLADE arises from its reliance on recombinases under the control of a single promoter, which integrates circuit signals on a single transcriptional layer. We used BLADE to build 113 circuits in human embryonic kidney and Jurkat T cells and devised a quantitative, vector-proximity metric to evaluate their performance. Of 113 circuits analyzed, 109 functioned (96.5%) as intended without optimization. The circuits, which are available through Addgene, include a 3-input, two-output full adder; a 6-input, one-output Boolean logic look-up table; circuits with small-molecule-inducible control; and circuits that incorporate CRISPR-Cas9 to regulate endogenous genes. BLADE enables execution of sophisticated cellular computation in mammalian cells, with applications in cell and tissue engineering.
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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.