Cotransfection of heme oxygenase-1 prevents the acute inflammation elicited by a second adenovirus.
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.
McCarter
S D
SD
Department of Medical Biophysics and Surgery, University of Western Ontario and the Lawson Health Research Institute, London, ON, Canada.
Scott
J R
JR
Lee
P J
PJ
Zhang
X
X
Choi
A M K
AM
McLean
C A
CA
Badhwar
A
A
Dungey
A A
AA
Bihari
A
A
Harris
K A
KA
Potter
R F
RF
D000208:Acute Disease; D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006505:Hepatitis / Q000276:immunology / Q000517:prevention & control*; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D008862:Microsomes, Liver / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods*
D008565:Membrane Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse