Journal
DIABETOLOGIA
Volume 54, Issue 5, Pages 1075-1086Publisher
SPRINGER
DOI: 10.1007/s00125-011-2070-3
Keywords
Adeno-associated vectors; Beta cells; Diabetes; Gene therapy; Gene transfer; Pancreas
Categories
Funding
- Ministerio de Ciencia e Innovacion
- Plan Nacional I+D+I [SAF2008-00962]
- Generalitat de Catalunya, Spain [2009 SGR-224]
- European Commission [LSHB-CT-2006-018933]
- Ministerio de Educacion, Cultura y Deporte
- Ministerio de Educacion
- Direccio General de Recerca, Generalitat de Catalunya, Spain
Ask authors/readers for more resources
The genetic engineering of pancreatic beta cells could be a powerful tool for examining the role of key genes in the cause and treatment of diabetes. Here we performed a comparative study of the ability of single-stranded (ss) adeno-associated viral vectors (AAV) of serotypes 6, 8 and 9 to transduce the pancreas in vivo. AAV6, AAV8 and AAV9 vectors encoding marker genes were delivered to the pancreas via intraductal or systemic administration. Transduced cells were analysed by immunostaining. AAV9 vectors encoding hepatocyte growth factor (HGF) were delivered intraductally to a transgenic mouse model of type 1 diabetes and glycaemia was monitored. AAV6, AAV8 and AAV9 mediated efficient and long-term transduction of beta cells, with AAV6 and AAV8 showing the highest efficiency. However, alpha cells were poorly transduced. Acinar cells were transduced by the three serotypes tested and ductal cells only by AAV6. In addition, intraductal delivery resulted in higher AAV-mediated transduction of the pancreas than did systemic administration. As proof of concept, intraductal delivery of AAV9 vectors encoding for the beta cell anti-apoptotic and mitogenic HGF preserved beta cell mass, diminished lymphocytic infiltration of the islets and protected mice from autoimmune diabetes. Intraductal administration of AAV6, AAV8 and AAV9 is an efficient way to genetically manipulate the pancreas in vivo. This technology may prove useful in the study of islet physiopathology and in assessment of new gene therapy approaches designed to regenerate beta cell mass during diabetes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available