dsAAV8-mediated gene transfer and ß-cell expression of IL-4 and ß-cell growth factors are capable of reversing early-onset diabetes in NOD mice.
Gene Ther
; 19(8): 791-9, 2012 Aug.
Article
in En
| MEDLINE
| ID: mdl-22089495
ABSTRACT
Type-I diabetes is a chronic disease mediated by autoimmune destruction of insulin-producing ß-cells. Although progress has been made towards improving diabetes-associated pathologies and the quality of life for those living with diabetes, no therapy has been effective at eliminating disease manifestations or reversing disease progression. Here, we examined whether double-stranded adeno-associated virus serotype 8 (dsAAV8)-mediated gene delivery to endogenous ß-cells of interleukin (IL)-4 in combination with ß-cell growth factors can reverse early-onset diabetes in NOD mice. Our results demonstrate that a single treatment with dsAAV8 vectors expressing IL-4 in combination with glucagon-like peptide-1 or hepatocyte growth factor/NK1 under the regulation of the insulin promoter enhanced ß-cell proliferation and survival in vivo, significantly delaying diabetes progression in NOD mice, and reversing disease in â¼10% of treated NOD mice. These results demonstrate the ability to reverse hyperglycemia in NOD mice with established diabetes by in vivo gene transfer to ß-cells of immunomodulatory factors and ß-cell growth factors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Therapy
/
Interleukin-4
/
Hepatocyte Growth Factor
/
Dependovirus
/
Diabetes Mellitus, Experimental
/
Diabetes Mellitus, Type 1
/
Insulin-Secreting Cells
/
Glucagon-Like Peptide 1
Aspects:
Patient_preference
Limits:
Animals
Language:
En
Journal:
Gene Ther
Journal subject:
GENETICA MEDICA
/
TERAPEUTICA
Year:
2012
Document type:
Article
Affiliation country:
United States