This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishi, T. Articles by Ushio, Y. Search for Related Content PubMed PubMed Citation Articles by Nishi, T. Articles by Ushio, Y.

High-Efficiency in Vivo Gene Transfer Using Intraarterial Plasmid DNA Injection following in Vivo Electroporation¹

Departments of Neurosurgery [T. N., K. Y., S. Y., K. S., K. H., I. K., J. K., Y. U.] and Tumor Genetics and Biology [H. S.], Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860, Japan, and Immunopathology Section, Laboratory of Immunobiology, National Cancer Institute, Frederick, Maryland 21702 [T. Y.]

A novel method for high-efficiency and region-controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery of rats whose brain tumors (from prior inoculation) had been electroporated between two electrodes. The lacZ gene was efficiently transferred and expressed in the tumor cells 3 days after plasmid injection. However, neither any gene transfers nor any elevated lacZ activity was detected in tissues outside the electrodes. The plasmid was not transferred without electroporation. Human monocyte chemoattractant protein-1 cDNA was also transferred by this method, and its long-lasting (3 weeks) expression was confirmed by using the Epstein-Barr virus episomal replicon system. The expressed monocyte chemoat-tractant protein-1 protein was functional, as evident by the presence of a large number of monocytes in the tumor tissue. This method, "electrogene therapy," which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy.

¹ This work was supported in part by the prize money of the first Hoshino Award and Grants-in-Aid from the Ministry of Education, Science and Culture of Japan (07557095).

² To whom requests for reprints should be addressed. Phone: 96-373-5219; Fax: 96-371-8064; E-mail: tnishi@gpo.kumamoto-u.ac.jp.

Received 9/25/95. Accepted 1/ 3/96.

This article has been cited by other articles:

				L. Zhang, L. Gao, Y. Li, G. Lin, Y. Shao, K. Ji, H. Yu, J. Hu, D. V. Kalvakolanu, D. J. Kopecko, et al. Effects of Plasmid-Based Stat3-Specific Short Hairpin RNA and GRIM-19 on PC-3M Tumor Cell Growth Clin. Cancer Res., January 15, 2008; 14(2): 559 - 568. [Abstract] [Full Text] [PDF]

				Y. Takei, T. Nemoto, P. Mu, T. Fujishima, T. Ishimoto, Y. Hayakawa, Y. Yuzawa, S. Matsuo, T. Muramatsu, and K. Kadomatsu In vivo silencing of a molecular target by short interfering RNA electroporation: tumor vascularization correlates to delivery efficiency Mol. Cancer Ther., January 1, 2008; 7(1): 211 - 221. [Abstract] [Full Text] [PDF]

				S. Sonoda, K. Tachibana, E. Uchino, A. Okubo, M. Yamamoto, K. Sakoda, T. Hisatomi, K.-H. Sonoda, Y. Negishi, Y. Izumi, et al. Gene Transfer to Corneal Epithelium and Keratocytes Mediated by Ultrasound with Microbubbles Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 558 - 564. [Abstract] [Full Text] [PDF]

				M. Kalat, Z. Kupcu, S. Schuller, D. Zalusky, M. Zehetner, W. Paster, and T. Schweighoffer In Vivo Plasmid Electroporation Induces Tumor Antigen-specific CD8+ T-Cell Responses and Delays Tumor Growth in a Syngeneic Mouse Melanoma Model Cancer Res., October 1, 2002; 62(19): 5489 - 5494. [Abstract] [Full Text] [PDF]

				E. Quint, A. Smith, F. Avaron, L. Laforest, J. Miles, W. Gaffield, and M.-A. Akimenko From the Cover: Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine PNAS, June 25, 2002; 99(13): 8713 - 8718. [Abstract] [Full Text] [PDF]

				K. Mikata, H. Uemura, H. Ohuchi, S. Ohta, Y. Nagashima, and Y. Kubota Inhibition of Growth of Human Prostate Cancer Xenograft by Transfection of p53 Gene: Gene Transfer by Electroporation Mol. Cancer Ther., February 1, 2002; 1(4): 247 - 252. [Abstract] [Full Text] [PDF]

				Y.-i. Yamashita, M. Shimada, H. Hasegawa, R. Minagawa, T. Rikimaru, T. Hamatsu, S. Tanaka, K. Shirabe, J.-i. Miyazaki, and K. Sugimachi Electroporation-mediated Interleukin-12 Gene Therapy for Hepatocellular Carcinoma in the Mice Model Cancer Res., February 1, 2001; 61(3): 1005 - 1012. [Abstract] [Full Text]

				S. Zucchelli, S. Capone, E. Fattori, A. Folgori, A. Di Marco, D. Casimiro, A. J. Simon, R. Laufer, N. La Monica, R. Cortese, et al. Enhancing B- and T-Cell Immune Response to a Hepatitis C Virus E2 DNA Vaccine by Intramuscular Electrical Gene Transfer J. Virol., December 15, 2000; 74(24): 11598 - 11607. [Abstract] [Full Text]

				G. Widera, M. Austin, D. Rabussay, C. Goldbeck, S. W. Barnett, M. Chen, L. Leung, G. R. Otten, K. Thudium, M. J. Selby, et al. Increased DNA Vaccine Delivery and Immunogenicity by Electroporation In Vivo J. Immunol., May 1, 2000; 164(9): 4635 - 4640. [Abstract] [Full Text] [PDF]

				T. Goto, T. Nishi, T. Tamura, S. B. Dev, H. Takeshima, M. Kochi, K. Yoshizato, J.-i. Kuratsu, T. Sakata, G. A. Hofmann, et al. Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene PNAS, January 4, 2000; 97(1): 354 - 359. [Abstract] [Full Text] [PDF]

				G. Rizzuto, M. Cappelletti, D. Maione, R. Savino, D. Lazzaro, P. Costa, I. Mathiesen, R. Cortese, G. Ciliberto, R. Laufer, et al. Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation PNAS, May 25, 1999; 96(11): 6417 - 6422. [Abstract] [Full Text] [PDF]

				Y. Yamazaki, H. Fujimoto, H. Ando, T. Ohyama, Y. Hirota, and T. Noce In Vivo Gene Transfer to Mouse Spermatogenic Cells by Deoxyribonucleic Acid Injection into Seminiferous Tubules and Subsequent Electroporation Biol Reprod, December 1, 1998; 59(6): 1439 - 1444. [Abstract] [Full Text]