Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene.
We report successful electro-gene therapy (EGT) by using plasmid DNA for tumor-bearing mice. Subcutaneously inoculated CT26 tumor was subjected to EGT, which consists of intratumoral injection of a naked plasmid encoding a marker gene or a therapeutic gene, followed by in vivo electroporation (EP). When this treatment modality is carried out with the plasmid DNA for the green fluorescent protein gene, followed by in vivo EP with the optimized pulse parameters, numerous intensely bright green fluorescent signals appeared within the tumor. EGT, by using the "A" fragment of the diphtheria toxin gene significantly inhibited the growth of tumors, by about 30%, on the flank of mice. With the herpes simplex virus thymidine kinase gene, followed by systemic injection of ganciclovir, EGT was far more effective in retarding tumor growth, varying between 50% and 90%, compared with the other controls. Based on these results, it appears that EGT can be used successfully for treating murine solid tumors.
Goto
T
T
Department of Neurosurgery, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
Nishi
T
T
Tamura
T
T
Dev
S B
SB
Takeshima
H
H
Kochi
M
M
Yoshizato
K
K
Kuratsu
J
J
Sakata
T
T
Hofmann
G A
GA
Ushio
Y
Y
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002455:Cell Division / Q000235:genetics; D017690:Cell Transplantation; D003110:Colonic Neoplasms; D004167:Diphtheria Toxin / Q000235:genetics; D004195:Disease Models, Animal; D018274:Electroporation / Q000379:methods*; D015774:Ganciclovir / Q000494:pharmacology; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins; D006651:Histocytochemistry; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics / Q000627:therapeutic use*; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D004167:Diphtheria Toxin; D005819:Genetic Markers; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir