Abstract
We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) vector encoding the human proinsulin gene under a constitutive liver specific promoter. In vivo dose titration experiments were carried out and we identified an optimal range that achieved maintenance of euglycaemia or a mild diabetic condition for at least 9 months and ongoing to beyond 1 year for some animals, accompanied by human C-peptide secretion and weight gain. Further DNA codon optimization of the insulin gene construct resulted in approximately 3-10 times more human C-peptide secreted in the blood of codon optimized treated animals thereby reducing the number of vector particles required to achieve the same extent of reduction in blood glucose levels as the non-codon optimized vector. The constitutive secretion of insulin achieved with a single administration of the vector could be of therapeutic value for some diabetic patients.
Keywords: Gene therapy, Diabetes, Insulin, AAV, Codon optimization.
Current Gene Therapy
Title:Correction of Murine Diabetic Hyperglycaemia With A Single Systemic Administration of An AAV2/8 Vector Containing A Novel Codon Optimized Human Insulin Gene
Volume: 16 Issue: 1
Author(s): Gan Shu Uin, Notaridou Maria, Fu Zhen Ying, Lee Kok Onn, Sia Kian Chuan, Nathwani Amit Chunilal, Della Peruta Marco and Calne Roy Yorke
Affiliation:
Keywords: Gene therapy, Diabetes, Insulin, AAV, Codon optimization.
Abstract: We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) vector encoding the human proinsulin gene under a constitutive liver specific promoter. In vivo dose titration experiments were carried out and we identified an optimal range that achieved maintenance of euglycaemia or a mild diabetic condition for at least 9 months and ongoing to beyond 1 year for some animals, accompanied by human C-peptide secretion and weight gain. Further DNA codon optimization of the insulin gene construct resulted in approximately 3-10 times more human C-peptide secreted in the blood of codon optimized treated animals thereby reducing the number of vector particles required to achieve the same extent of reduction in blood glucose levels as the non-codon optimized vector. The constitutive secretion of insulin achieved with a single administration of the vector could be of therapeutic value for some diabetic patients.
Export Options
About this article
Cite this article as:
Uin Shu Gan, Maria Notaridou, Ying Zhen Fu, Kok Onn Lee, Chuan Kian Sia, Chunilal Amit Nathwani, Marco Peruta Della and Yorke Roy Calne, Correction of Murine Diabetic Hyperglycaemia With A Single Systemic Administration of An AAV2/8 Vector Containing A Novel Codon Optimized Human Insulin Gene, Current Gene Therapy 2016; 16 (1) . https://dx.doi.org/10.2174/1566523216666160122113958
DOI https://dx.doi.org/10.2174/1566523216666160122113958 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Inpatient Diabetes Management in Non-ICU Settings: Evidence and Strategies
Current Diabetes Reviews Pancreatic β-Cells and Type 2 Diabetes Development
Current Diabetes Reviews Glycation and Antioxidants: Hand in the Glove of Antiglycation and Natural Antioxidants
Current Protein & Peptide Science Preparation of Hymenialdisine, Analogues and Their Evaluation as Kinase Inhibitors
Current Medicinal Chemistry Targeting the Eph System with Peptides and Peptide Conjugates
Current Drug Targets Advanced Techniques for Imaging the Human Spinal Cord: Review of Literature
Current Medical Imaging <i>Laurus Nobilis</i> Linn. Inhibits Polyol Pathway Enzymes: Strategy for Managing Diabetic Complications
Current Enzyme Inhibition Insight on the Pathogenesis of Diabetic Nephropathy from the Study of Podocyte and Mesangial Cell Biology
Current Diabetes Reviews Immunotherapy-Based Strategies for the Treatment of Autoimmune Diabetes: Searching for the Cure
Current Pharmaceutical Design Non-Steroidal Anti-Inflammatory Drugs as Anti-Amyloidogenic Compounds
Current Pharmaceutical Design Parkinson's Disease: From Genetics to Clinical Practice
Current Genomics Central Arterial Aging and Angiotensin II Signaling
Current Hypertension Reviews Synthesis, Crystal Structure, Anti-inflammatory and Anti-hyperglycemic Activities of Novel 3,4-Disubstituted 1,2,4-Triazol-5(4H)-one Derivatives
Medicinal Chemistry The Potential Role of Glycogen Synthase Kinase 3 Inhibitors as Amyotrophic Lateral Sclerosis Pharmacological Therapy
Current Medicinal Chemistry Targeting Epigenetics in Nervous System Disease
CNS & Neurological Disorders - Drug Targets Patent Selections:
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) The beneficial effect of Cape gooseberry juice on carbon tetrachloride-induced neuronal damage
CNS & Neurological Disorders - Drug Targets Pathophysiology of Transmissible Spongiform Encephalopathies
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Metabolic Syndrome X is a Low-Grade Systemic Inflammatory Condition with its Origins in the Perinatal Period
Current Nutrition & Food Science Peripheral Arterial Disease in Persons with Diabetic Foot Ulceration: a Current Comprehensive Overview
Current Diabetes Reviews