Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer.
This study demonstrates in vivo effectiveness of a nonviral vector system, Epstein-Barr virus (EBV)-based plasmid vector coupled with polyamidoamine (PAMAM) dendrimer (EBV/polyplex), in suicide gene therapy of cancer. The EBV-based vector is a plasmid vector containing EBV nuclear antigen 1 (EBNA1) gene and oriP from EBV genome. HSV-1 tk gene was transferred into Ewing's sarcoma cell lines, A4573 and KP-EWS-YI, by using an EBV-based plasmid vector, pSES.Tk, or a conventional plasmid vector, pS.Tk. Cells transfected with pSES.Tk/dendrimer showed approximately 100 times lower ID50 to ganciclovir (GCV) compared with those transfected with pS. Tk/dendrimer. Intratumoral injection of pSES.Tk/dendrimer but not pS. Tk/dendrimer drastically suppressed the growth of tumors which had generated from A4573 or Huh7 hepatocellular carcinoma (HCC) cells inoculated into severe combined immunodeficiency (SCID) mice. The treatment with pSES.Tk/dendrimer also resulted in significant prolongation of survival of the mice implanted with A4573. These results suggest that the EBV/polyplex system could be useful for in vivo suicide gene therapy of cancer. Gene Therapy (2000) 7, 53-60.
Maruyama-Tabata
H
H
Department of Pediatrics, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan.
Harada
Y
Y
Matsumura
T
T
Satoh
E
E
Cui
F
F
Iwai
M
M
Kita
M
M
Hibi
S
S
Imanishi
J
J
Sawada
T
T
Mazda
O
O
D000818:Animals; D050091:Dendrimers; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D011073:Polyamines; D012512:Sarcoma, Ewing / Q000628:therapy*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection / Q000235:genetics
D050091:Dendrimers; D019309:Epstein-Barr Virus Nuclear Antigens; C104700:PAMAM Starburst; D011073:Polyamines; D013937:Thymidine Kinase