Biolistic-mediated interleukin 4 gene transfer prevents the onset of type 1 diabetes.
We tested the efficacy of biolistic-mediated gene transfer as a noninvasive therapy for type 1 diabetes (T1D) in nonobese diabetic (NOD) mice by expression of murine interleukin 4 (mIL-4) cDNA. Epidermal delivery of 2 microg of DNA yielded transient detection of serum mIL-4, using a conventional cDNA expression vector. A vector stabilized by incorporation of the Epstein-Barr virus (EBV) EBNA1/oriP episomal maintenance replicon produced higher levels of serum mIL-4 that persisted for 12 days after inoculation. Although biolistic inoculation of either vector reduced insulitis and prevented diabetes, the protracted mIL-4 expression afforded by the EBV vector resulted in Th2-type responses in the periphery and pancreas and more significant protection from the onset of diabetes. Our studies demonstrate the efficacy of biolistic gene delivery of stabilized cytokine expression as a viable therapeutic approach to prevent the onset of T1D.
Cameron
M J
MJ
Autoimmunity/Diabetes Group, John P. Robarts Research Institute, London, Ontario, Canada. Canada.
Strathdee
C A
CA
Holmes
K D
KD
Arreaza
G A
GA
Dekaban
G A
GA
Delovitch
T L
TL
D000818:Animals; D019470:Biolistics; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000235:genetics; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
D016207:Cytokines; D018076:DNA, Complementary; D015847:Interleukin-4; D007073:Immunoglobulin E