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.
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