Biolistic-mediated interleukin 4 gene transfer prevents the onset of type 1 diabetes

Hum Gene Ther. 2000 Aug 10;11(12):1647-56. doi: 10.1089/10430340050111304.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biolistics*
  • Cytokines / analysis
  • Cytokines / metabolism
  • DNA, Complementary / genetics
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Female
  • Flow Cytometry
  • Genetic Vectors
  • Herpesvirus 4, Human / genetics
  • Immunoglobulin E / blood
  • Interleukin-4 / genetics*
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred NOD
  • Pancreas / metabolism
  • Pancreas / pathology
  • T-Lymphocytes / metabolism

Substances

  • Cytokines
  • DNA, Complementary
  • Interleukin-4
  • Immunoglobulin E