ArticleThe journal of gene medicine2019
Development of a liver-specific Tet-off AAV8 vector for improved safety of insulin gene therapy for diabetes.
Article in The journal of gene medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- The Role of Gene Therapy and RNA-Based Therapeutic Strategies in Diabetes.International journal of molecular sciences · 2025Review
- Maturity-Onset Diabetes of the Young 10 (MODY10): A Comprehensive Review of Genetics, Clinical Features, and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Recombinant adeno-associated virus 8 vector in gene therapy: Opportunities and challenges.Genes & diseases · 2024Review
- Generation of a Beta-Cell Transplant Animal Model of Diabetes Using CRISPR Technology.Advances in experimental medicine and biology · 2023Article
- Codon-optimized FAM132b gene therapy prevents dietary obesity by blockading adrenergic response and insulin action.International journal of obesity (2005) · 2022Article
- First use of gene therapy to treat growth hormone resistant dwarfism in a mouse model.Gene therapy · 2022Article
- Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era.Journal of translational medicine · 2021Review
- Article
- CRISPR-mediated BMP9 ablation promotes liver steatosis via the down-regulation of PPARα expression.Science advances · 2020Article
- Article
- Development of a liver-specific Tet-off AAV8 vector for improved safety of insulin gene therapy for diabetes.The journal of gene medicine · 2019Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetes mellitus is caused by a partial or complete lack of insulin production in the body. We have previously shown that a single injection of an adeno-associated virus serotype 8 (AAV8) vector carrying a modified and codon optimized human insulin gene induced hepatic production of insulin and corrected streptozotocin (STZ)-induced diabetes in mice for more than 1 year. Insulin production was constitutive, analogous to long-acting insulin therapy.
methodsWe have developed a single AAV8 vector with a Tet-Off regulatable system as a safety mechanism to turn off insulin secretion should hypoglycaemia develop in vector-treated diabetic mice. We first transfected HepG2 cells or freshly isolated rat hepatocytes in vitro with the Tet-Off system (pAAV-Tetoff
resultsUsing STZ-induced diabetic mice, we were able to switch off insulin secretion repeatedly with doxycycline administration, and showed full restoration of insulin secretion on withdrawing doxycycline.
conclusionsThe present study provides proof of concept that, under circumstances when inappropriate basal insulin secretion is a safety concern, insulin secretion from AAV8 gene therapy can be turned off reversibly with doxycycline.
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