DsAAV8-mediated gene transfer and Β-cell expression of IL-4 and Β-cell growth factors are capable of reversing early-onset diabetes in NOD mice

D. F. Gaddy, M. J. Riedel, S. Bertera, T. J. Kieffer, P. D. Robbins

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Type-I diabetes is a chronic disease mediated by autoimmune destruction of insulin-producing β-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 Β-cells of interleukin (IL)-4 in combination with Β-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 Β-cell proliferation and survival in vivo, significantly delaying diabetes progression in NOD mice, and reversing disease in 10% of treated NOD mice. These results demonstrate the ability to reverse hyperglycemia in NOD mice with established diabetes by in vivo gene transfer to Β-cells of immunomodulatory factors and β-cell growth factors.

Original languageEnglish (US)
Pages (from-to)791-799
Number of pages9
JournalGene therapy
Issue number8
StatePublished - Aug 2012
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a program grant from the Juvenile Diabetes Research Foundation (JDRF) to PDR, and DFG was supported by a fellowship from the JDRF. MJR was supported by the Michael Smith Foundation for Health Research (MSFHR), the Canadian Diabetes Association, the Stem Cell Network and the JDRF. TJK is a MSFHR senior scholar. We thank Maliha Zahid (University of Pittsburgh) for assistance with statistical analysis and Joan Nash (University of Pittsburgh) for assistance with microscopy analysis.

Copyright 2012 Elsevier B.V., All rights reserved.


  • adeno-associated virus
  • glucagon-like peptide-1
  • hepatocyte growth factor
  • interleukin-4
  • type-I diabetes

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