ArticleProceedings of the National Academy of Sciences of the United States of America2008
A synthetic mammalian gene circuit reveals antituberculosis compounds.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 159 citations in OpenAlex.
- Alpibectir-Ethionamide combination (AlpE) for the treatment of tuberculosis.Nature communications · 2026Article
- A Gene-Switch Platform Interfacing with Reactive Oxygen Species Enables Transcription Fine-Tuning by Soluble and Volatile Pharmacologics and Food Additives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Therapeutic applications of synthetic gene/genetic circuits: a patent review.Frontiers in bioengineering and biotechnology · 2024Review
- Synthetic biology-inspired cell engineering in diagnosis, treatment, and drug development.Signal transduction and targeted therapy · 2023Review
- Plant synthetic epigenomic engineering for crop improvement.Science China. Life sciences · 2022Review
- Antimicrobial Peptides Controlling Resistant Bacteria in Animal Production.Frontiers in microbiology · 2022Review
- 5-Fluorouracil blocks quorum-sensing of biofilm-embedded methicillin-resistant Staphylococcus aureus in mice.Nucleic acids research · 2021Article
- Small-molecule inducible transcriptional control in mammalian cells.Critical reviews in biotechnology · 2020Review
- Synthetic Biology Speeds Up Drug Target Discovery.Frontiers in pharmacology · 2020Review
- Synthetic Biology Based on Genetic Logic Circuit, Using the Expression of Drug Resistance, BCRP Pump in MCF-7 Cancer Cell Line.Iranian journal of pharmaceutical research : IJPR · 2020Article
- Preparation of Celery Essential Oil-Based Nanoemulsion by Ultrasonication and Evaluation of Its Potential Anticancer and Antibacterial Activity.International journal of nanomedicine · 2020Article
- Transcriptional programming using engineered systems of transcription factors and genetic architectures.Nature communications · 2019Article
- Review
- Anti-myeloma activity and molecular logic operation by Natural Killer cells in microfluidic droplets.Sensors and actuators. B, Chemical · 2019Article
- Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics.Progress in biophysics and molecular biology · 2019Review
- Sigma Factor-Mediated Tuning of Bacterial Cell-Free Synthetic Genetic Oscillators.ACS synthetic biology · 2018Article
- A synthetic free fatty acid-regulated transgene switch in mammalian cells and mice.Nucleic acids research · 2018Article
- Designing cell function: assembly of synthetic gene circuits for cell biology applications.Nature reviews. Molecular cell biology · 2018Review
- Designer cells programming quorum-sensing interference with microbes.Nature communications · 2018Article
- A synthetic biology-based device prevents liver injury in mice.Journal of hepatology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic biology provides insight into natural gene-network dynamics and enables assembly of engineered transcription circuitries for production of difficult-to-access therapeutic molecules. In Mycobacterium tuberculosis EthR binds to a specific operator (O(ethR)) thereby repressing ethA and preventing EthA-catalyzed conversion of the prodrug ethionamide, which increases the resistance of the pathogen to this last-line-of-defense treatment. We have designed a synthetic mammalian gene circuit that senses the EthR-O(ethR) interaction in human cells and produces a quantitative reporter gene expression readout. Challenging of the synthetic network with compounds of a rationally designed chemical library revealed 2-phenylethyl-butyrate as a nontoxic substance that abolished EthR's repressor function inside human cells, in mice, and within M. tuberculosis where it triggered derepression of ethA and increased the sensitivity of this pathogen to ethionamide. The discovery of antituberculosis compounds by using synthetic mammalian gene circuits may establish a new line of defense against multidrug-resistant M. tuberculosis.
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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.