Cotransfection of heme oxygenase-1 prevents the acute inflammation elicited by a second adenovirus

• Published in: Gene therapy Vol. 10; no. 19; pp. 1629 - 1635
• Main Authors: MCCARTER, S. D, SCOTT, J. R, POTTER, R. F, LEE, P. J, ZHANG, X, CHOI, A. M. K, MCLEAN, C. A, BADHWAR, A, DUNGEY, A. A, BIHARI, A, HARRIS, K. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-09-2003
• Subjects: Acute Disease; Adenoviridae - genetics; Adenoviridae - immunology; Adenoviruses; Animals; Biological and medical sciences; Care and treatment; Enzymes; Expression vectors; Gene expression; Gene therapy; Genetic Therapy - methods; Genetic vectors; Genetic Vectors - administration & dosage; Genetic Vectors - immunology; Health aspects; Hematologic and hematopoietic diseases; Heme; Heme oxygenase (decyclizing); Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase-1; Hepatitis - immunology; Hepatitis - prevention & control; Inflammation; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Liver - immunology; Liver - virology; Male; Medical sciences; Membrane Proteins; Methods; Mice; Mice, Inbred C57BL; Microscopy, Video; Microsomes, Liver - enzymology; Oxygenase; Physiological aspects; Reverse Transcriptase Polymerase Chain Reaction; Risk factors; Transfection; Transfection - methods; Vectors (Biology); Canada; heme oxygenase; Adenoviridae; intravital microscopy; Enzyme; Liver; Inflammation; Virus; Oxygenase; Transfection; Heme; adenovirus; Oxidoreductases; Gene therapy; Vector
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302063

The acute inflammatory response elicited by adenovirus vectors results in loss of gene expression and tissue injury in the target organ. This acute inflammation is now believed to be the major limiting factor for the use of adenovirus vectors in gene therapy. While exploring the level of acute inflammation caused by the adenovirus encoding the gene for the anti-inflammatory enzyme heme oxygenase-1, we discovered that this adenovirus not only did not elicit acute inflammation, but could prevent the inflammation caused by a second adenovirus. Here we describe a new approach to gene therapy, which uses the encoding of the potent anti-inflammatory enzyme heme oxygenase-1 to prevent early host inflammatory responses normally associated with adenovirus vectors.