Increased Hepatic Transduction with Reduced Systemic Dissemination and Proinflammatory Cytokines Following Hydrodynamic Injection of Helper-Dependent Adenoviral Vectors

doi:doi:10.1016/j.ymthe.2005.03.001

Molecular Therapy (2005) 12, 99–106; doi: 10.1016/j.ymthe.2005.03.001

Increased Hepatic Transduction with Reduced Systemic Dissemination and Proinflammatory Cytokines Following Hydrodynamic Injection of Helper-Dependent Adenoviral Vectors

Nicola Brunetti-Pierri¹, Donna J. Palmer¹, Viraj Mane¹, Milton Finegold², Arthur L. Beaudet¹ and Philip Ng¹

¹Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX77030, USA
²Department of Pathology, Baylor College of Medicine, Houston, TX77030, USA

Correspondence: Ng Philip, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, T619, Houston, TX77030, USA. Fax: +1 713 798 7773. E-mail: png@bcm.tmc.edu.

Received 23 February 2005; Accepted 3 March 2005.

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Abstract

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.