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Mol Ther. 2005 Jul;12(1):99-106.

Increased hepatic transduction with reduced systemic dissemination and proinflammatory cytokines following hydrodynamic injection of helper-dependent adenoviral vectors.

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Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.


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.

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