ArticleProceedings of the National Academy of Sciences of the United States of America2013
Pharmaceutically controlled designer circuit for the treatment of the metabolic syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 100 citations in OpenAlex.
- JP-14: A Trace Amine-Associated Receptor 1 Agonist with Anti-Metabolic Disorder Potential.International journal of molecular sciences · 2025Article
- A sensitive red/far-red photoswitch for controllable gene therapy in mouse models of metabolic diseases.Nature communications · 2024Article
- Engineered IRES-mediated promoter-free insulin-producing cells reverse hyperglycemia.Frontiers in endocrinology · 2024Article
- Metabolic and cardiovascular benefits and risks of 4-hydroxy guanabenz hydrochloride: αPharmacological reports : PR · 2023Article
- Applications of synthetic biology in medical and pharmaceutical fields.Signal transduction and targeted therapy · 2023Review
- Performance Prediction of Fundamental Transcriptional Programs.ACS synthetic biology · 2023Article
- Controlling therapeutic protein expression via inhalation of a butter flavor molecule.Nucleic acids research · 2023Article
- Emerging technologies for genetic control systems in cellular therapies.Current opinion in biotechnology · 2022Review
- Article
- Biomarker-driven feedback control of synthetic biology systems for next-generation personalized medicine.Frontiers in bioengineering and biotechnology · 2022Review
- Gene-circuit therapy on the horizon: synthetic biology tools for engineered therapeutics.Acta biochimica Polonica · 2021Review
- A synthetic BRET-based optogenetic device for pulsatile transgene expression enabling glucose homeostasis in mice.Nature communications · 2021Article
- Building sophisticated sensors of extracellular cues that enable mammalian cells to work as "doctors" in the body.Cellular and molecular life sciences : CMLS · 2020Review
- Administration of small-molecule guanabenz acetate attenuates fatty liver and hyperglycemia associated with obesity.Scientific reports · 2020Article
- Synthetic Biology Speeds Up Drug Target Discovery.Frontiers in pharmacology · 2020Review
- Promises of Nanotherapeutics in Obesity.Trends in endocrinology and metabolism: TEM · 2019Review
- Genetic circuits to engineer tissues with alternative functions.Journal of biological engineering · 2019Review
- Bottom-up approaches in synthetic biology and biomaterials for tissue engineering applications.Journal of industrial microbiology & biotechnology · 2018Article
- Generalized extracellular molecule sensor platform for programming cellular behavior.Nature chemical biology · 2018Article
- Caffeine-inducible gene switches controlling experimental diabetes.Nature communications · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic biology has significantly advanced the design of genetic devices that can reprogram cellular activities and provide novel treatment strategies for future gene- and cell-based therapies. However, many metabolic disorders are functionally linked while developing distinct diseases that are difficult to treat using a classic one-drug-one-disease intervention scheme. For example, hypertension, hyperglycemia, obesity, and dyslipidemia are interdependent pathologies that are collectively known as the metabolic syndrome, the prime epidemic of the 21st century. We have designed a unique therapeutic strategy in which the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin. Therefore, the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements. Based on this designer signaling cascade, it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin, a bifunctional therapeutic peptide hormone that combines the glucagon-like peptide 1 (GLP-1) and leptin via an IgG-Fc linker. In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia. Using a clinically licensed drug to coordinate expression of therapeutic transgenes combines drug- and gene-based therapies for coordinated treatment of functionally related metabolic disorders.
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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.