Purpose
To evaluate the tissue-specific characteristics of electric gene transfer after tissue and intravenous injection of naked plasmid DNA (pDNA).
Methods
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.
Results
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.
Conclusions
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.
Similar content being viewed by others
References
I. Danko P. Williams H. Herweijer G. Zhang J. S. Latendresse I. Bock J. A. Wolff (1997) ArticleTitleHigh expression of naked plasmid DNA in muscles of young rodents Hum. Mol. Genet. 6 1435–1443 Occurrence Handle1:CAS:528:DyaK2sXlvVGjs70%3D Occurrence Handle9285779
S. Chesnoy L. Huang (2002) ArticleTitleEnhanced cutaneous gene delivery following intradermal injection of naked DNA in a high ionic strength solution Molec. Ther. 5 57–62 Occurrence Handle1:CAS:528:DC%2BD38XhvFGqtb4%3D
M. A. Hickman R. W. Malone K. Lehmann-Bruinsma T. R. Sih D. Knoell F. C. Szoka R. Walzem D. M. Carlson J. S. Powell (1994) ArticleTitleGene expression following direct injection of DNA into liver Hum. Gene Ther. 5 1477–1483 Occurrence Handle1:CAS:528:DyaK2MXjsVWmurc%3D Occurrence Handle7711140
Y. Taniyama R. Morishita M. Aoki H. Nakagami K. Yamamoto K. Yamazaki K. Matsumoto T. Nakamura Y. Kaneda T. Ogihara (2001) ArticleTitleTherapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease Gene Ther. 8 181–189 Occurrence Handle1:CAS:528:DC%2BD3MXht1GmtLg%3D Occurrence Handle11313789
N. Sarkar A. Rück G. Källner S. Y-Hassan P. Blomberg K. B. Islam J. Linden ParticleVan Der D. Lindblom A. T. Nygren B. Lind L. Å. Brodin V. Drvota C. Sylvén (2001) ArticleTitleEffects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease-12-month follow-up: angiogenic gene therapy J. Intern. Med. 250 373–381 Occurrence Handle1:CAS:528:DC%2BD3MXovFCqu7c%3D Occurrence Handle11887971
S. Somiari J. Glasspool-Malone J. J. Drabick R. A. Gilbert R. Heller M. J. Jaroszeski R. W. Malone (2000) ArticleTitleTheory and in vivo application of electroporative gene delivery Molec. Ther. 2 178–187 Occurrence Handle1:CAS:528:DC%2BD38XhvF2ht78%3D
D. A. Zaharoff R. C. Barr C. Y. Li F. Yuan (2002) ArticleTitleElectromobility of plasmid DNA in tumor tissues during electric field-mediated gene delivery Gene Ther. 9 1286–1290 Occurrence Handle1:CAS:528:DC%2BD38XmvVGjsLg%3D Occurrence Handle12224011
H. Maruyama K. Ataka N. Higuchi F. Sakamoto F. Gejyo J. Miyazaki (2001) ArticleTitleSkin-targeted gene transfer using in vivo electroporation Gene Ther. 8 1808–1812 Occurrence Handle1:CAS:528:DC%2BD38XmvVeltg%3D%3D Occurrence Handle11803401
T. Suzuki B. C. Shin K. Fujikura T. Matsuzaki K. Takata (1998) ArticleTitleDirect gene transfer into rat liver cells by in vivo electroporation FEBS Lett. 425 436–440 Occurrence Handle1:CAS:528:DyaK1cXitVKhsrk%3D Occurrence Handle9563509
M. Bettan F. Emmanuel R. Darteil J. M. Caillaud F. Soubrier P. Delaere D. Branelec A. Mahfoudi N. Duverger D. Scherman (2000) ArticleTitleHigh-level protein secretion into blood circulation after electric pulse-mediated gene transfer into skeletal muscle Molec. Ther. 2 204–210 Occurrence Handle1:CAS:528:DC%2BD38XhvF2ht7o%3D
I. Mathiesen (1999) ArticleTitleElectropermeabilization of skeletal muscle enhances gene transfer in vivo Gene Ther. 6 508–514 Occurrence Handle1:CAS:528:DyaK1MXit1Omu7k%3D Occurrence Handle10476210
J. Glasspool-Malone S. Somiari J. J. Drabick R. W. Malone (2000) ArticleTitleEfficient nonviral cutaneous transfection Molec. Ther. 2 140–146 Occurrence Handle1:CAS:528:DC%2BD38XhvF2hsb8%3D
M. Hashida M. Nishikawa F. Yamashita Y. Takakura (2001) ArticleTitleCell-specific delivery of genes with glycosylated carriers Adv. Drug Deliv. Rev. 52 187–196 Occurrence Handle1:CAS:528:DC%2BD3MXosFKltLg%3D Occurrence Handle11718943
F. Liu Y. Song D. Liu (1999) ArticleTitleHydrodynamics-based transfection in animals by systemic administration of plasmid DNA Gene Ther. 6 1258–1266 Occurrence Handle1:CAS:528:DyaK1MXksVKht74%3D Occurrence Handle10455434
G. Zhang V. Budker J. A. Wolff (1999) ArticleTitleHigh levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA Hum. Gene Ther. 10 1735–1737 Occurrence Handle1:CAS:528:DyaK1MXksVejtrc%3D Occurrence Handle10428218
V. Budker G. Zhang I. Danko P. Williams J. A. Wolff (1998) ArticleTitleThe efficient expression of intravascularly delivered DNA in rat muscle Gene Ther. 5 272–276 Occurrence Handle1:CAS:528:DyaK1cXhtFOltrk%3D Occurrence Handle9578848
K. W. Liang M. Nishikawa F. Liu B. Sun Q. Ye L. Huang (2004) ArticleTitleRestoration of dystrophin expression in mdx mice by intravascular injection of naked DNA containing full-length dystrophin cDNA Gene Ther. 11 901–908 Occurrence Handle1:CAS:528:DC%2BD2cXktVGjsLk%3D Occurrence Handle14985786
H. Herweijer J. A. Wolff (2003) ArticleTitleProgress and prospects: naked DNA gene transfer and therapy Gene Ther. 10 453–458 Occurrence Handle1:CAS:528:DC%2BD3sXhs1yhtrk%3D Occurrence Handle12621449
F. Liu L. Huang (2002) ArticleTitleElectric gene transfer to the liver following systemic administration of plasmid DNA Gene Ther. 9 1116–1119 Occurrence Handle1:CAS:528:DC%2BD38XlsFOmtbc%3D Occurrence Handle12140740
M. Sakai M. Nishikawa O. Thanaketpaisarn F. Yamashita M. Hashida (2005) ArticleTitleHepatocyte-targeted gene transfer by combination of vascularly delivery plasmid DNA and in vivo electroporation Gene Ther. 12 607–616 Occurrence Handle1:CAS:528:DC%2BD2MXisFKiurk%3D Occurrence Handle15616599
M. Nishikawa M. Hashida (2002) ArticleTitleNonviral approaches satisfying various requirements for effective in vivo gene therapy Biol. Pharm. Bull. 25 275–283 Occurrence Handle1:CAS:528:DC%2BD38XkslWltrw%3D Occurrence Handle11913519
C. H. Miao A. R. Thompson K. Loeb X. Ye (2001) ArticleTitleLong-term and therapeutic-level hepatic gene expression of human factor IX after naked plasmid transfer in vivo Molec. Ther. 3 947–957 Occurrence Handle1:CAS:528:DC%2BD38XhvFKitL4%3D
D. A. Roth N. E. Tawa SuffixJr. J. M. O’Brien D. A. Treco R. F. Selden (2001) ArticleTitleNon-viral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia A N. Engl. J. Med. 344 1735–1742 Occurrence Handle1:CAS:528:DC%2BD3MXkslKqsbw%3D Occurrence Handle11396439
J. M. Wang H. Zheng M. Blaivas K. Kurachi (1997) ArticleTitlePersistent systemic production of human factor IX in mice by skeletal myoblast-mediated gene transfer: feasibility of repeat application to obtain therapeutic levels Blood 90 1075–1082 Occurrence Handle1:CAS:528:DyaK2sXkvVWgsrk%3D Occurrence Handle9242538
N. Kobayashi T. Kuramoto K. Yamaoka M. Hashida Y. Takakura (2001) ArticleTitleHepatic uptake and gene expression mechanisms following intravenous administration of plasmid DNA by conventional and hydrodynamics-based procedures J. Pharmacol. Exp. Ther. 297 853–860 Occurrence Handle1:CAS:528:DC%2BD3MXjvVSiurw%3D Occurrence Handle11356904
K. Kawabata Y. Takakura M. Hashida (1995) ArticleTitleThe fate of plasmid DNA after intravenous injection in mice: involvement of scavenger receptors in its hepatic uptake Pharm. Res. 12 825–830 Occurrence Handle1:CAS:528:DyaK2MXmtV2qurc%3D Occurrence Handle7667185
M. Nishikawa L. Huang (2001) ArticleTitleNonviral vectors in the new millennium: delivery barriers in gene transfer Hum. Gene Ther. 12 861–870 Occurrence Handle1:CAS:528:DC%2BD3MXktVWhtr0%3D Occurrence Handle11387052
D. Guo T. Fu J. A. Nelson R. A. Superina H. E. Soriano (2002) ArticleTitleLiver repopulation after cell transplantation in mice treated with retrorsine and carbon tetrachloride Transplantation 73 1818–1824 Occurrence Handle1:CAS:528:DC%2BD38XlslClsbc%3D Occurrence Handle12085007
J. A. Wolff J. J. Ludtke G. Acsadi P. Williams A. Jani (1992) ArticleTitleLong-term persistence of plasmid DNA and foreign gene expression in mouse muscle Hum. Mol. Genet. 1 363–369 Occurrence Handle1:CAS:528:DyaK38Xmt1Ogtr0%3D Occurrence Handle1301910
E. Fattori N. L. Monica G. Ciliberto C. Toniatti (2002) ArticleTitleElectro-gene-transfer: a new approach for muscle gene delivery Somat. Cell Mol. Genet. 27 75–83 Occurrence Handle1:CAS:528:DC%2BD3sXitlCjtLw%3D Occurrence Handle12774942
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)
A. J. O’hara J. M. Howell R. H. Taplin S. Fletcher F. Lloyd B. Kakulas H. Lochmuller G. Karpati (2001) ArticleTitleThe spread of transgene expression at the site of gene construct injection Muscle Nerve 24 488–495 Occurrence Handle1:STN:280:DC%2BD3M7ntVSrsg%3D%3D Occurrence Handle11268020
Y. Takakura R. I. Mahato M. Hashida (1998) ArticleTitleExtravasation of macromolecules Adv. Drug Deliv. Rev. 34 93–108 Occurrence Handle1:CAS:528:DyaK1cXmvFWis74%3D Occurrence Handle10837672
N. Kobayashi M. Nishikawa K. Hirata Y. Takakura (2004) ArticleTitleHydrodynamics-based procedure involves transient hyperpermeability in the hepatic cellular membrane: implication of a nonspecific process in efficient intracellular gene delivery J. Gene Med. 6 584–592 Occurrence Handle1:CAS:528:DC%2BD2cXlt1Cmtr0%3D Occurrence Handle15133769
M. Tsujie Y. Isaka H. Nakamura E. Imai M. Hori (2001) ArticleTitleElectroporation-mediated gene transfer that targets glomeruli J. Am. Soc. Nephrol. 12 949–954 Occurrence Handle1:CAS:528:DC%2BD3MXjvVCgtL0%3D Occurrence Handle11316853
J. M. Vicat S. Boisseau P. Jourdes M. Laine D. Wion R. Bouali-Benazzouz A. L. Benabid F. Berger (2000) ArticleTitleMuscle transfection by electroporation with high-voltage and short-pulse currents provides high-level and long-lasting gene expression Hum. Gene Ther. 11 909–916 Occurrence Handle1:CAS:528:DC%2BD3cXisFOksbY%3D Occurrence Handle10779167
D. A. Dean D. Machado-Aranda1 K. Blair-Parks A. V. Yeldandi J. L. Young (2003) ArticleTitleElectroporation as a method for high-level nonviral gene transfer to the lung Gene Ther. 10 1608–1615 Occurrence Handle1:CAS:528:DC%2BD3sXmtV2nsLk%3D Occurrence Handle12907953
Acknowledgments
This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Thanaketpaisarn, O., Nishikawa, M., Yamashita, F. et al. Tissue-Specific Characteristics of in Vivo Electric Gene: Transfer by Tissue and Intravenous Injection of Plasmid DNA. Pharm Res 22, 883–891 (2005). https://doi.org/10.1007/s11095-005-4583-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-005-4583-2