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International Journal of Experimental Diabetes Research
Volume 2 (2001), Issue 2, Pages 129-138
http://dx.doi.org/10.1155/EDR.2001.129

Prevention of Diabetes in the NOD Mouse by Intra-muscular Injection of Recombinant Adeno-associated Virus Containing the Preproinsulin II Gene

1Department of Surgery, Indiana University School of Medicine, Indianapolis, USA
2Department of Surgery, University of Glasgow, Glasgow G11 6NT, UK

Received 17 January 2001; Revised 14 April 2001; Accepted 29 May 2001

Copyright © 2001 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Using the Adeno-associated virus (AAV) as a gene delivery vehicle, we have constructed a recombinant vector containing the full length rat preproinsulin gene (vLP-1). Utilizing the well described non-obese diabetic (NOD) mouse model, an experimental group (n=10) of animals were intramuscularly (IM) injected with 107 rAAV virions containing the insulin gene and compared to a mock-injected control group (n=10). Blood glucose (glc) was then measured weekly for 16 weeks. Data showed that the experimental group contained 70% euglycemic animals (defined as glc <200mg/dL) versus 10% of the control animals (P<.05) at 14 weeks. Mean weight in the treated group was greater than the untreated group. Insulin mRNA was detected at the injection site of all of the treated animals, but not controls. Complete destruction of islets was confirmed by histology ruling out the possibility of spontaneous reversal of insulinitis. We conclude that IM delivery of the insulin gene in the NOD mouse was able to prevent clinical DM up to 14 weeks in a majority of treated animals. Our experimental data suggests that gene therapy may be an alternative treatment for IDDM in the future.