Development of an inflammation-inducible gene expression system using helper-dependent adenoviral vectors

Abstract

Background: Clinical studies have shown that gene therapy is a promising approach for treating such genetic diseases as the eye disease, Leber's congenital amaurosis. Development of gene therapy approaches for treating chronic inflammatory diseases is, however, more challenging because it requires the production of anti-inflammatory molecules at the diseased tissues only when they are needed. Methods: We designed such a system by modifying the human interleukin (IL)-6 gene promoter to direct transgene expression and delivered the system into cultured cells as well as mouse lungs using a helper-dependent adenoviral vector. Results: We have demonstrated both in vitro and in vivo that the reporter LacZ or human IL-10 gene can be induced by inflammatory stimuli. Conclusions: The results obtained indicate that the inflammation inducible gene expression system based on the modified human IL-6 gene promoter has the potential to be used for developing gene therapy for treating inflammatory diseases. © 2010 John Wiley & Sons, Ltd.