Acknowledgements

Figure 5. Scheme of the computer-controlled hydrodynamic injection system. Prior to an injection, a user selects appropriate time-pressure pattern for delivery and preload the data to the command unit. The command unit transmits the data to the control unit, which modulates electric power based on the feedback information of an intravascular pressure during

Figure 6. Image-guided, computer-controlled HGD to the dog liver. The balloon catheter was placed at the appropriate position in the hepatic veins of right lateral lobe and the occlusion of the blood flow by the balloon was confirmed by injecting a small amount of contrast medium into the hepatic vein. Then the hydrodynamic injection of naked DNA solution was performed under the real time monitoring of liver structure by the laparoscope using the computercontrolled injection system (A). (B) Time-pressure curve and the volume of injected solution recorded in the injection system. Solid and dotted lines represent actual and preloaded time-pressure curves. The gray area shows cumulative volume of injected saline (ml). (C) Laparoscopic findings of the hydrodynamically injected right lateral lobe of the dog. The injected lobe was swollen, and the injected DNA solution transiently made the liver pale. Neither destruction nor bleeding was seen on the surface of the liver (arrowheads). (D) The effect of lobe-specific hydrodynamic gene delivery of luciferase expressing plasmid. (i) Liver samples were collected by needle biopsy under the ultrasound sonography 4 days after the injection. (ii) The immunohistochemical analyses showed positively stained cells in the injected right lateral lobe. No stained cells were found in noninjected left lateral lobe. This figure is partly reused and modified with updated

the injection from the pressure sensor placed at the peripheral vein of a target area.

12 In Vivo and Ex Vivo Gene Therapy for Inherited and Non-Inherited Disorders

information from Figure 1 in [58] with their permission.

This work was supported in part by grant-in-aid for scientific research from the Japanese Society for the Promotion of Sciences, 16K19333 to Yokoo T, 17K09408 to Kamimura.

This work has finished due to Dexi Liu, and all members at Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University. The authors would like to appreciate all members at the Niigata city industrial promotion center and for their excellent assistance in producing the system, Yoshihiko Ohba for the supporting of finetuning of the system.
