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

• Published in: The journal of gene medicine Vol. 12; no. 10; pp. 832 - 839
• Main Authors: Yang, Tianyao, Duan, Rongqi, Cao, Huibi, Lee, Benjamin H., Xia, Chun, Chang, Zhijie, Keith Tanswell, A., Hu, Jim
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.2010; Wiley Periodicals Inc
• Subjects: Adenoviridae - genetics; Adenoviridae - metabolism; airway; Animals; Bronchi - cytology; Cell Line; Cell Line, Tumor; Cells, Cultured; chronic inflammatory diseases; Female; Gene Expression; Gene therapy; Gene Transfer Techniques; Genetic Therapy - methods; Genetic Vectors; Helper Viruses - genetics; helper-dependent adenoviral vector; Humans; Inflammation - genetics; inflammation-inducible expression; interleukin-10; Interleukin-10 - genetics; Interleukin-6 - genetics; Lac Operon; Lung - pathology; Mice; Mice, Inbred C57BL; Promoter Regions, Genetic; Transfection; Transgenes
• ISSN: 1099-498X; 1521-2254; 1521-2254
• DOI: 10.1002/jgm.1501

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. Copyright © 2010 John Wiley & Sons, Ltd.