利用含有新密码子优化的人胰岛素原基因的单次假腺相关病毒8型（AAV2/8）载体给药进行全身给药，对STZ诱导糖尿病小鼠高血糖进行校正

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 and Nathwani Amit Chunilal, Della Peruta Marco and Calne Roy Yorke

Affiliation:

关键词: 基因治疗，糖尿病，胰岛素，AAV，密码子优化。

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.

Cite this article as:

Gan Shu Uin, Notaridou Maria, Fu Zhen Ying, Lee Kok Onn, Sia Kian Chuan and Nathwani Amit Chunilal, Della Peruta Marco and Calne Roy Yorke , 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