GENE-THERAPY FOR THE TREATMENT OF HEPATOMA BY RETROVIRAL-MEDIATED GENE-TRANSFER OF THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE

被引:20
作者
KURIYAMA, S [1 ]
YOSHIKAWA, M [1 ]
TOMINAGA, K [1 ]
NAKATANI, T [1 ]
SAKAMOTO, T [1 ]
FUKUI, H [1 ]
IKENAKA, K [1 ]
TSUJII, T [1 ]
机构
[1] NATL INST PHYSIOL SCI,NEURAL INFORMAT LAB,OKAZAKI,AICHI 444,JAPAN
来源
INTERNATIONAL HEPATOLOGY COMMUNICATIONS | 1993年 / 1卷 / 05期
关键词
GENE THERAPY; HEPATOMA; RETROVIRAL VECTOR; HERPES SIMPLEX VIRUS; THYMIDINE KINASE; LIVER-SPECIFIC PROMOTER; GANCICLOVIR;
D O I
10.1016/0928-4346(93)90072-N
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
We previously demonstrated that a foreign gene transferred by means of a retroviral vector can be expressed selectively in hepatoma cells when a liver-specific promoter was used to direct its expression. We now describe an approach for the treatment of hepatoma by the introduction of herpes simplex virus thymidine kinase (HSV-TK) gene. Expression of HSV-TK gene in hepatoma cells was evaluated as an elimination system for a potential use in therapies. A murine retroviral vector was constructed in which the HSV-TK gene was expressed under control of the murine albumin enhancer and promoter elements. Replication-defective vector viral particles were obtained by transfer of the vector DNA into the ecotropic packaging cell line psi2 and were used to infect murine hepatoma cells. The introduction of the HSV-TK gene into hepatoma cells by infection of the recombinant retrovirus did not affect their proliferation at all. The sensitivity of those infected cells to the toxic effects of the nucleoside analog ganciclovir was found to be significantly increased by transfer of the HSV-TK gene. The difference in sensitivity between infected and uninfected cells to ganciclovir concentrations should give the utility for a clinical application, indicating the feasibility of gene therapy toward hepatoma by the retroviral-mediated HSV-TK gene transfer.
引用
收藏
页码:253 / 259
页数:7
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