Minimal Invasive Technique for Gene Delivery in Porcine Liver Lobe Segment

ABSTRACT

Introduction: The feasibility and outcome of large volume injection of gene solution in a segment of a liver lobe, without backflow, were studied in a porcine model, using a custom-designed balloon catheter. Method: Eight anesthetized pigs underwent successful injection of 200 ml of gene solution at a rate of 20 ml/s via a minimally invasive technique without backflow. A custom-made balloon catheter was introduced under fluoroscopy guidance into the right lateral liver lobe via the right external jugular vein. The vein of the liver lobe was occluded with the balloon catheter and contrast material was injected to check if total occlusion was achieved. Since there was no backflow an angiographic pump injected the solution. The catheter was left in place for 10 min. Then contrast material was injected to check whether the vein remained occluded. Results: All animals tolerated the procedure without obvious adverse effects. Ultrasound scan showed no gross changes within liver three days following the infusion. A transient rise in platelet count was observed which returned to normal after 13 days and remained stable; all other biochemistry values were normal. Conclusions: Injecting large volume of gene solution in a liver lobe segment using this minimally invasive technique in a porcine model is possible, making the development of a successful gene transfer protocol in humans feasible.

Keywords: :

• hydrodynamic gene therapy
• minimal invasive technique
• porcine model
• liver
• fluoroscopy
• infusion