ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
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- Comprehensive multiscale analysis of lactate metabolic dynamics in vitro and in vivo using highly responsive biosensors.Nature protocols · 2024Article
- Engineering natural molecule-triggered genetic control systems for tunable gene- and cell-based therapies.Synthetic and systems biotechnology · 2023Article
- Design of programmable post-translational switch control platform for on-demand protein secretion in mammalian cells.Nucleic acids research · 2023Article
- Therapeutic cell engineering: designing programmable synthetic genetic circuits in mammalian cells.Protein & cell · 2022Review
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- A small and highly sensitive red/far-red optogenetic switch for applications in mammals.Nature biotechnology · 2022Article
- Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Engineering genetic devices for in vivo control of therapeutic T cell activity triggered by the dietary molecule resveratrol.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Smart-watch-programmed green-light-operated percutaneous control of therapeutic transgenes.Nature communications · 2021Article
- Engineering Mammalian Cells to Control Glucose Homeostasis.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Small-molecule inducible transcriptional control in mammalian cells.Critical reviews in biotechnology · 2020Review
- A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate.Science advances · 2020Article
- A non-invasive far-red light-induced split-Cre recombinase system for controllable genome engineering in mice.Nature communications · 2020Article
- Potential Protective Effect of Oleanolic Acid on the Components of Metabolic Syndrome: A Systematic Review.Journal of clinical medicine · 2019Review
- Programmable and printable Bacillus subtilis biofilms as engineered living materials.Nature chemical biology · 2019Article
- Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders. Here, we utilized the congruent pharmacological activities of OA and glucagon-like-peptide 1 (GLP-1) in relieving IR and improving liver and pancreas functions and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs. In particular, OA-triggered short human GLP-1 (shGLP-1) expression in hepatogenous diabetic mice rapidly and simultaneously attenuated many disease-specific metabolic failures, whereas OA or shGLP-1 monotherapy failed to achieve corresponding therapeutic effects. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficacies of single therapeutics.
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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.