Hydrodynamics-based gene delivery to the liver by bile duct injection of plasmid DNA--the impact of lasting biliary obstruction and injection volume.

BACKGROUND/AIMS: Increased biliary pressure may mediate an opening of intrahepatic tight junctions. The biliary pressure is related to the duration of biliary obstruction and the injected volume. Their effects on the efficiency of gene delivery to the liver were studied.
METHODOLOGY: The luciferase gene with a volume of 0.5, 1.0, 1.5 or 2.0mL was injected into the bile duct of Sprague-Dawley rats. After the injection, the bile ducts were occluded in some of the rats, while left to drain in the others.
RESULTS: The activity of luciferase was the highest in rats that received 2.0mL of DNA injection and biliary occlusion, while the lowest in the rats that received 0.5mL of DNA only.
CONCLUSIONS: The bile duct can be an efficient route for gene delivery to the liver depending on the volume of injected DNA. Biliary occlusion can enhance the expression of genes but it may induce a certain degree of liver injury, which should be taken into concern.