Increased hepatic transduction with reduced systemic dissemination and proinflammatory cytokines following hydrodynamic injection of helper-dependent adenoviral vectors.
Hydrodynamic injection of helper-dependent adenoviral vectors (HDAd) in mice results in increased hepatic transduction, reduced splenic and pulmonary transduction, and reduced levels of the proinflammatory cytokines IL-6 and IL-12 compared to conventional injection. These results indicate that hepatic transduction by HDAd, at least alone, does not necessarily provoke a severe innate inflammatory response. Instead, they suggest that systemic vector dissemination may play a major role in the severity of the innate inflammatory response. These results further suggest that the safety and efficacy of HDAd-mediated, liver-directed gene therapy may be improved if the vector could be preferentially, if not exclusively, targeted to liver.
Brunetti-Pierri
Nicola
N
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Palmer
Donna J
DJ
Mane
Viraj
V
Finegold
Milton
M
Beaudet
Arthur L
AL
Ng
Philip
P
D000256:Adenoviridae; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005164:Factor IX / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D019076:Transgenes
D016207:Cytokines; D005164:Factor IX