Hydroporation as the mechanism of hydrodynamic delivery.
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.
Zhang
G
G
Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261, USA.
Gao
X
X
Song
Y K
YK
Vollmer
R
R
Stolz
D B
DB
Gasiorowski
J Z
JZ
Dean
D A
DA
Liu
D
D
D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure; D002196:Capillaries / Q000648:ultrastructure; D048429:Cell Size; D004562:Electrocardiography; D015870:Gene Expression; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006339:Heart Rate; D022781:Hepatocytes / Q000378:metabolism* / Q000648:ultrastructure; D007275:Injections, Intravenous; D008107:Liver Diseases / Q000628:therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D014162:Transfection / Q000379:methods*