Application of in vivo electroporation to cancer gene therapy.
Much intensive research has gone into the development of safe and efficient methods for the delivery of therapeutic genes. In vivo electroporation is a non-viral delivery protocol in which plasmid DNA solutions are injected into targeted tissues, followed by electric pulses (typically 100 V, 50 ms). In general, in vivo electroporation enhances gene expression in targeted tissues by 2-3 orders of magnitude, as compared to the injection of plasmid DNA solutions without electric pulses, and the tissue damage appears to be minimal. Among the other advantages of this technique are that it can safely be administered repeatedly, and it is simpler and more economical to use than viral vectors, especially in clinical cases. Using this approach, highly efficient gene transfer has already been achieved in muscle and liver as well as in tumors. In fact, gene therapies for cancer utilizing in vivo electroporation have been proved effective in a number of experimental murine tumor models. The therapeutic genes delivered in those cases were diverse including, for example, cytokine genes (IL-12) and cytotoxic genes (TRAIL), making possible a wide range of therapeutic strategies. Moreover, systemic antitumor effects were also observed, suggesting that this approach may be effective for the treatment of metastatic as well as primary tumors.
Tamura
Takahiko
T
Division of Molecular Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2- B7 Yamadaoka, Suita, Osaka 565-0871, Japan. tamura@onbich.med.osaka-u.ac.jp
Sakata
Tsuneaki
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D018274:Electroporation; D015316:Genetic Therapy; D018664:Interleukin-12 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12