ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Remission of diabetes by insulin gene therapy using a hepatocyte-specific and glucose-responsive synthetic promoter.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 47 citations in OpenAlex.
- Gene therapy in cardiac and vascular diseases: a review of approaches to treat genetic and common cardiovascular diseases with novel gene-based therapeutics.Cardiovascular research · 2025Review
- Article
- Generation of a Beta-Cell Transplant Animal Model of Diabetes Using CRISPR Technology.Advances in experimental medicine and biology · 2023Article
- Therapeutic Advances in Diabetes, Autoimmune, and Neurological Diseases.International journal of molecular sciences · 2021Review
- Lentivirus Mediated Pancreatic Beta-Cell-Specific Insulin Gene Therapy for STZ-Induced Diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Article
- Efficacy of insulin targeted gene therapy for type 1 diabetes mellitus: A systematic review and meta-analysis of rodent studies.Iranian journal of basic medical sciences · 2020Review
- An Ecdysone Receptor-based Singular Gene Switch for Deliberate Expression of Transgene with Robustness, Reversibility, and Negligible Leakiness.Journal of visualized experiments : JoVE · 2018Article
- Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs.Molecular therapy. Methods & clinical development · 2017Article
- Ecdysone Receptor-based Singular Gene Switches for Regulated Transgene Expression in Cells and Adult Rodent Tissues.Molecular therapy. Nucleic acids · 2016Article
- Glucose-regulated insulin production in the liver improves glycemic control in type 1 diabetic mice.Molecular metabolism · 2015Article
- The use of β-cell transcription factors in engineering artificial β cells from non-pancreatic tissue.Gene therapy · 2015Review
- Role of insulin in the type 2 diabetes therapy: past, present and future.International journal of endocrinology and metabolism · 2013Review
- Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice.World journal of gastroenterology · 2012Article
- Synthetic biology: advancing biological frontiers by building synthetic systems.Genome biology · 2012Review
- Animal models of diabetes mellitus for islet transplantation.Experimental diabetes research · 2012Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Efficient production of insulin in response to changes in glucose levels has been a major issue for insulin gene therapy to treat diabetes. To express target genes in response to glucose specifically in hepatocytes, we generated a synthetic promoter library containing hepatocyte nuclear factor-1, CAAT/enhancer-binding protein (C/EBP) response element, and glucose-response element. Combinations of these three cis-elements in 3-, 6-, or 9-element configurations were screened for transcriptional activity and then glucose responsiveness in vitro. The most effective promoter (SP23137) was selected for further study. Intravenous administration of a recombinant adenovirus expressing furin-cleavable rat insulin under control of the SP23137 promoter into streptozotocin (STZ)-induced diabetic mice resulted in normoglycemia, which was maintained for >30 days. Glucose tolerance tests showed that treated mice produced insulin in response to glucose and cleared exogenous glucose from the blood in a manner similar to nondiabetic control mice, although the clearance was somewhat delayed. Insulin expression was seen specifically in the liver and not in other organs. These observations indicate the potential of this synthetic, artificial promoter to regulate glucose-responsive insulin production and remit hyperglycemia, thus providing a new method of liver-directed insulin gene therapy for type 1 diabetes.
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