Development of an inflammation-inducible gene expression system using helper-dependent adenoviral vectors.
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.
Yang
Tianyao
T
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Duan
Rongqi
R
Cao
Huibi
H
Lee
Benjamin H
BH
Xia
Chun
C
Chang
Zhijie
Z
Keith Tanswell
A
A
Hu
Jim
J
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006378:Helper Viruses / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics*; D007763:Lac Operon; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D014162:Transfection; D019076:Transgenes
D015850:Interleukin-6; D016753:Interleukin-10