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Title: | Correction of Murine Diabetic Hyperglycaemia With A Single Systemic Administration of An AAV2/8 Vector Containing A Novel Codon Optimized Human Insulin Gene | Authors: | Uin, Gan Shu Maria, Notaridou Ying, Fu Zhen Onn, Lee Kok Chuan, Sia Kian Chunilal, Nathwani Amit Marco, Della Peruta Yorke, Calne Roy |
Keywords: | Science & Technology Life Sciences & Biomedicine Genetics & Heredity Gene therapy Diabetes Insulin AAV Codon optimization LONG-TERM SAFETY GLYCEMIC CONTROL HEMOPHILIA-B THERAPY EXPRESSION RATS MICE HEPATOCYTES FIBROBLASTS REVERSAL |
Issue Date: | 1-Jan-2016 | Publisher: | BENTHAM SCIENCE PUBL LTD | Citation: | Uin, Gan Shu, Maria, Notaridou, Ying, Fu Zhen, Onn, Lee Kok, Chuan, Sia Kian, Chunilal, Nathwani Amit, Marco, Della Peruta, Yorke, Calne Roy (2016-01-01). 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 16 (1) : 65-72. ScholarBank@NUS Repository. | 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. | Source Title: | CURRENT GENE THERAPY | URI: | https://scholarbank.nus.edu.sg/handle/10635/205938 | ISSN: | 15665232 18755631 |
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