ArticleProceedings of the National Academy of Sciences of the United States of America2016
Cellular heterogeneity mediates inherent sensitivity-specificity tradeoff in cancer targeting by synthetic circuits.
Article in Proceedings of the National Academy of Sciences of the United States of America, 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.
- Modular Scalable Synthetic Gene Circuits for Complex Functions Within Minimal Computational Layers in Human Cells.Nature communications · 2026Article
- Optimized pipeline and designer cells for synthetic-biology-based high-throughput screening of viral protease inhibitors.Cell reports methods · 2025Article
- Modeling ncRNA-Mediated Circuits in Cell Fate Decision: From Systems Biology to Synthetic Biology.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Synthetic Circuit-Driven Expression of Heterologous Enzymes for Disease Detection.ACS synthetic biology · 2021Article
- Design of Multipartite Transcription Factors for Multiplexed Logic Genome Integration Control in Mammalian Cells.ACS synthetic biology · 2020Article
- The intersectional genetics landscape for humans.GigaScience · 2020Article
- Programmable Synthetic Protein Circuits for the Identification and Suppression of Hepatocellular Carcinoma.Molecular therapy oncolytics · 2020Article
- Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapy.Nature communications · 2019Article
- Dual-microRNA-controlled double-amplified cascaded logic DNA circuits for accurate discrimination of cell subtypes.Chemical science · 2019Article
- Building with intent: technologies and principles for engineering mammalian cell-based therapies to sense and respond.Current opinion in biomedical engineering · 2017Article
- Article
- Designed cell consortia as fragrance-programmable analog-to-digital converters.Nature chemical biology · 2017Article
- Mammalian synthetic biology for studying the cell.The Journal of cell biology · 2017Review
- Synthetic Gene Expression Circuits for Designing Precision Tools in Oncology.Frontiers in cell and developmental biology · 2017Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic gene circuits are emerging as a versatile means to target cancer with enhanced specificity by combinatorial integration of multiple expression markers. Such circuits must also be tuned to be highly sensitive because escape of even a few cells might be detrimental. However, the error rates of decision-making circuits in light of cellular variability in gene expression have so far remained unexplored. Here, we measure the single-cell response function of a tunable logic AND gate acting on two promoters in heterogeneous cell populations. Our analysis reveals an inherent tradeoff between specificity and sensitivity that is controlled by the AND gate amplification gain and activation threshold. We implement a tumor-mimicking cell-culture model of cancer cells emerging in a background of normal ones, and show that molecular parameters of the synthetic circuits control specificity and sensitivity in a killing assay. This suggests that, beyond the inherent tradeoff, synthetic circuits operating in a heterogeneous environment could be optimized to efficiently target malignant state with minimal loss of specificity.
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