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.
