Gene Therapy with Plasmids Encoding Cytokine- or Cytokine Receptor-IgG Chimeric Proteins

Cytokine therapy can influence the outcome of autoimmune diseases by altering either T-helper 1 (Th1) vs T-helper 2 (Th2) balance or antigen-presenting cell (APC) function, or by shifting the balance between inflammatory and regulatory cytokines (1 ). However, cytokine and soluble cytokine-receptor therapy have been limited by the short half-life (T1/2) of these proteins and the necessity to administer relatively large boluses of recombinant proteins (2 ). This results in transient high systemic levels and, in the case of cytokines, toxicity and poor therapeutic efficiency. The in vivo blockade of cytokine function by monoclonal antibody therapy, although feasible, has also faced therapeutic limitations (3 ). Moreover, the isolation and production of highly purified and stable therapeutic proteins is laborious and expensive. Gene therapy has significant advantages, allowing long-term and relatively constant delivery of cytokines or their receptors at therapeutic levels. This can be accomplished with viral gene therapy vectors, as well as plasmid DNA expression vectors (nonviral approach). Our laboratory has been particularly interested in the delivery of vectors encoding cytokines and cytokine receptors for the prevention or treatment of autoimmune diseases.