Tissue-Specific Characteristics of in Vivo Electric Gene: Transfer by Tissue and Intravenous Injection of Plasmid DNA
- 201 Downloads
To evaluate the tissue-specific characteristics of electric gene transfer after tissue and intravenous injection of naked plasmid DNA (pDNA).
pDNA encoding firefly luciferase was injected directly into the liver, kidney, spleen, skin and muscle, or into the tail vein of mice, and electric pulses were then applied to one of these organs. The distribution of transgene expressing cells was evaluated using pDNA encoding β-galactosidase.
Tissue injection of pDNA produced a significant degree of transgene expression in any tissue with the greatest amount in the liver, followed by kidney and spleen. The expression in these organs decreased quickly with time, and muscle showed the greatest expression at 7 days. Electroporation significantly increased the expression, and the expression level was comparable among the organs. Intravenous injection of pDNA followed by electroporation resulted in a significant expression in the liver, spleen, and kidney but not in the skin or muscle.
Electric gene transfer to the liver, kidney, and spleen can be an effective approach to obtain significant amounts of transgene expression by either tissue or intravenous injection of pDNA, whereas it is only effective after tissue injection as far as skin- or muscle-targeted gene transfer is concerned.
Key wordselectroporation gene transfer intravascular injection plasmid DNA tissue distribution.
This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
- 2.Chesnoy, S., Huang, L. 2002Enhanced cutaneous gene delivery following intradermal injection of naked DNA in a high ionic strength solutionMolec. Ther.55762Google Scholar
- 4.Taniyama, Y., Morishita, R., Aoki, M., Nakagami, H., Yamamoto, K., Yamazaki, K., Matsumoto, K., Nakamura, T., Kaneda, Y., Ogihara, T. 2001Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial diseaseGene Ther.8181189PubMedGoogle Scholar
- 5.Sarkar, N., Rück, A., Källner, G., Y-Hassan, S., Blomberg, P., Islam, K. B., Linden, J., Lindblom, D., Nygren, A. T., Lind, B., Brodin, L. Å., Drvota, V., Sylvén, C. 2001Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease-12-month follow-up: angiogenic gene therapyJ. Intern. Med.250373381PubMedGoogle Scholar
- 6.Somiari, S., Glasspool-Malone, J., Drabick, J. J., Gilbert, R. A., Heller, R., Jaroszeski, M. J., Malone, R. W. 2000Theory and in vivo application of electroporative gene deliveryMolec. Ther.2178187Google Scholar
- 10.Bettan, M., Emmanuel, F., Darteil, R., Caillaud, J. M., Soubrier, F., Delaere, P., Branelec, D., Mahfoudi, A., Duverger, N., Scherman, D. 2000High-level protein secretion into blood circulation after electric pulse-mediated gene transfer into skeletal muscleMolec. Ther.2204210Google Scholar
- 12.Glasspool-Malone, J., Somiari, S., Drabick, J. J., Malone, R. W. 2000Efficient nonviral cutaneous transfectionMolec. Ther.2140146Google Scholar
- 22.Miao, C. H., Thompson, A. R., Loeb, K., Ye, X. 2001Long-term and therapeutic-level hepatic gene expression of human factor IX after naked plasmid transfer in vivoMolec. Ther.3947957Google Scholar
- 31.E. Tupin, B. Poirier, M. F. Bureau, J. Khallou-Laschet, R. Vranckx, G. Caligiuri, A. T. Gaston, J. P. Duong, V. Huyen, D. Scherman, J. Bariéty, J. B. Michel, and A. Nicoletti. Non-viral gene transfer of murine spleen cells achieved by in vivo electroporation. Gene Ther. 10:569–579 (2003)Google Scholar