1. ¹Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA
2. ²Division of Pathology, NSABP Foundation, Inc., Four Allegheny Center, Pittsburgh, PA, USA
3. ³Cell Biology and Physiology, Center for Biologic Imagine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4. ⁴Division of Pulmonary and Critical Care Medicine, College of Medicine, Northwestern University, Chicago, IL, USA

Correspondence: D Liu, Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, 527 Salk Hall, Pittsburgh, PA 15261, USA

Received 22 August 2003; Accepted 30 October 2003; Published online 15 January 2004.

Abstract

We have reported that a rapid tail vein injection of a large volume of plasmid DNA solution into a mouse results in high level of transgene expression in the liver. Gene transfer efficiency of this hydrodynamics-based procedure is determined by the combined effect of a large volume and high injection speed. Here, we show that the hydrodynamic injection induces a transient irregularity of heart function, a sharp increase in venous pressure, an enlargement of liver fenestrae, and enhancement of membrane permeability of the hepatocytes. At the cellular level, our results suggest that hepatic delivery by the hydrodynamic injection is accomplished by the generation of membrane pores in the hepatocytes.