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 expre ssion of murine interleukin 4 (mIL-4) cDNA, Epidermal delivery of 2 mu g 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 level s of serum mIL-4 that persisted for 12 days after inoculation. Although bio listic inoculation of either vector reduced insulitis and prevented diabete s, the protracted mIL-4 expression afforded by the EBV vector resulted in T h2-type responses in the periphery and pancreas and more significant protec tion from the onset of diabetes. Our studies demonstrate the efficacy of bi olistic gene delivery of stabilized cytokine expression as a viable therape utic approach to prevent the onset of T1D.