We investigated the delivery of foreign genes into mouse (MG) mouse model system. Highly efficient delivery was glioma cells in vivo using hemagglutinating virus of Japan observed in disseminated glioma cells, and 80% of MG (HVJ)-liposomes, which are coated by Sendai virus envelmice expressing the HSVtk gene were cured by treatment ope protein. HVJ-liposomes, containing lacZ gene or herwith ganciclovir. These results suggest that this novel gene pes simplex virus thymidine kinase (HSVtk) gene-bearing delivery system may be applicable for the in vivo gene therplasmid DNA were applied in the meningeal gliomatosis apy of human malignant glioma.Keywords: malignant glioma; gene transfer; HVJ-liposome; meningeal dissemination; MG mouseIt has been reported that intravenous administration of Introduction liposomes containing the rat insulin I gene resulted in Malignant glioma, especially glioblastoma, is one of the transient expression of rat insulin. 7 However, the most intractable tumors. Patients with glioblastoma have efficiency of liposomal fusion was low. The fusion a median survival of 9 months, despite intensive therapy efficiency was subsequently improved by using spike which may include surgery, irradiation, chemotherapy, proteins 8 or virus particles of HVJ. 9 HVJ-liposomes, and immunotherapy. 1 Poor prognosis is mainly due to which are coated by HVJ (Sendai virus) membranes, are invasion of glioma cells into the brain parenchyma. Morehighly fusigenic. HVJ-liposomes may contain DNA, and over, meningeal dissemination, the invasion of glioma using this system foreign genes can be transferred very cells into the cerebrospinal fluid, is observed in 15% of efficiently ( Figure 1) and expressed ectopically in dividglioma patients at their terminal stages and may also play ing or nondividing mammalian cells in vivo. [10][11][12][13] To date, a role in the poor prognosis of patients. 2 there have been few applications of HVJ-liposomes to We have used the meningeal gliomatosis (MG) mouse tumor therapy. In this study, HVJ-liposomes which conas a model system for patients with glioma. This model tain the lacZ gene or the HSVtk gene-bearing proviral system has been resistant to therapeutic intervention.DNA are applied in the MG mouse model, and we invesHowever, if 25% of stereotactically inoculated intratigate the efficacy of this delivery system for malignant cranial glioma cells are transduced with the herpes simglioma. plex virus type 1 thymidine kinase (HSVtk) gene, all mice can be cured by ganciclovir treatment. 3 Several methods exist for delivering foreign genes into somatic cells. Among them, retroviral vectors have been clinically one of the most frequently used. Because of low infectious titers, however, retroviruses have been used mainly for ex vivo gene delivery to hematopoietic stem cells, 4 or retrovirus-producing cells have been implanted in vivo as a source of continuous production. 5,6 Survival in the MG model could be prolonged by intrathecal administration of HSVtk-producing retrovirus packaging cell...