胰岛素原
全身给药
胰岛素
遗传增强
糖尿病
载体(分子生物学)
基因
腺相关病毒
体内
内分泌学
医学
内科学
重组DNA
生物
病毒学
遗传学
作者
Gan Shu Uin,Notaridou Maria,Fu Zhen Ying,Kok-Onn Lee,Kian Chuan Sia,Nathwani Amit Chunilal,Marco Della Peruta,Calne Roy Yorke
标识
DOI:10.2174/1566523216666160122113958
摘要
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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