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Long-term, antidiabetogenic effects of GLP-1 gene therapy using a double-stranded, adeno-associated viral vector

Authors
 S H Choi  ;  H C Lee 
Citation
 GENE THERAPY, Vol.18(2) : 155-163, 2011 
Journal Title
GENE THERAPY
ISSN
 0969-7128 
Issue Date
2011
MeSH
Animals ; Blood Glucose/analysis ; DNA* ; Dependovirus/genetics* ; Diabetes Mellitus, Experimental/therapy* ; GeneticTherapy/methods* ; Genetic Vectors ; Glucagon-Like Peptide 1/genetics* ; Glucagon-Like Peptide 1/metabolism ; Male ; Mice ; Mice, Obese
Keywords
glucagon-like peptide-1 ; GLP-1 ; diabetes ; adeno-associated virus ; dsAAV
Abstract
Diabetes is characterized by insulin resistance and a reduction in insulin secretion, leading to progressive β-cell failure and loss of β-cell mass. Its central therapeutic issues are how to restore glucose responsiveness of β-cells to normal and counteract defects in insulin secretion. Native glucagon-like peptide-1 (GLP-1), which makes β-cells competent and diabetic β-cells specifically more sensitive to glucose, has a major drawback of rapid inactivation. In this study, we describe the construction and analysis of a GLP-1 plasmid and double-stranded, adeno-associated viral (dsAAV) expression vector to overcome both the rapid degradation of native GLP-1 and limitations of gene therapy using standard single-stranded AAV. Our study results demonstrate that fasting blood glucose levels of db/db obese mice decreased significantly up to 4 months after a single injection of dsAAV GLP-1, and both insulin and circulating GLP-1 levels increased in dsAAV GLP-1-infected mice. These results demonstrate that dsAAV GLP-1 has long-term, efficient transgene expression with minimal toxicity and cellular immune responses. This study suggests that GLP-1 produced by dsAAV may be an alternative to the continuous infusions required for GLP-1 peptide therapy or daily injections of GLP-1.
Full Text
http://www.nature.com/gt/journal/v18/n2/full/gt2010119a.html
DOI
10.1038/gt.2010.119
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Hyun Chul(이현철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94142
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