Computer-assisted hydrodynamic gene delivery.
The recently developed hydrodynamic delivery method makes it possible to deliver DNA and RNA into parenchyma cells by intravascular injection of nucleic acid-containing solution. While this procedure is effective in rodents, it is difficult to perform in large animals, because manual control while delivering the injection cannot be sufficiently reliable for achieving a just-right hydrodynamic pressure in targeted tissue. In order to overcome this problem, we have developed a computer-controlled injection device that uses real-time intravascular pressure as a regulator. Using the new injection device, and mouse liver as the model organ, we demonstrated continuous injection at a single pressure and different pressures, and also serial (repeated) injections at intervals of 250 ms, by programming the computer according to the need. When assessed by reporter plasmids, the computer-controlled injection device exhibits gene delivery efficiency similar to that of conventional hydrodynamic injection. The device is also effective in gene delivery to kidney and muscle cells in rats, with plasmids or adenoviral vectors as gene carriers. Successful gene delivery to liver and kidney was also demonstrated in pigs, with the computer-controlled injection being combined with image-guided catheterization. These results represent a significant advance in in vivo gene delivery research, with potential for use in gene therapy in humans.
Suda
Takeshi
T
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Suda
Kieko
K
Liu
Dexi
D
D000818:Animals; D003201:Computers; D004247:DNA / Q000378:metabolism*; D004867:Equipment Design; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000295:instrumentation* / Q000379:methods*; D005822:Genetic Vectors; D007668:Kidney / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D051381:Rats; D012984:Software; D013552:Swine; D014584:User-Computer Interface
D012313:RNA; D004247:DNA