Tissue-specific characteristics of in vivo electric gene: transfer by tissue and intravenous injection of plasmid DNA.
OBJECTIVE
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 beta-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.
Thanaketpaisarn
Oranuch
O
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Nishikawa
Makiya
M
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D004247:DNA / Q000235:genetics*; D004566:Electrodes; D018274:Electroporation; D005260:Female; D005697:Galactosides; D005821:Genetic Techniques; D006651:Histocytochemistry; D007211:Indoles; D007275:Injections, Intravenous; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000235:genetics*; D014018:Tissue Distribution; D019076:Transgenes
D005697:Galactosides; D007211:Indoles; D004247:DNA; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside