INVIVO GENE-TRANSFER WITH RETROVIRAL VECTOR PRODUCER CELLS FOR TREATMENT OF EXPERIMENTAL BRAIN-TUMORS
INVIVO GENE-TRANSFER WITH RETROVIRAL VECTOR PRODUCER CELLS FOR TREATMENT OF EXPERIMENTAL BRAIN-TUMORS
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DOI：
10.1126/science.1317968
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发表时间：
1992-06-12
期刊：
影响因子：
56.9
通讯作者：
BLAESE, RM
中科院分区：
文献类型：
--
作者：
CULVER, KW;RAM, Z;BLAESE, RM
将外源基因直接原位导入增殖期肿瘤可为局部肿瘤的治疗提供一种有效的方法。给患有脑胶质瘤的大鼠瘤内立体定位注射鼠成纤维细胞，这些成纤维细胞产生逆转录病毒载体，其中插入了单纯疱疹病毒胸苷激酶（HS-tk）基因。5天后，在此期间，原位产生的HS-tk逆转录病毒载体转导邻近的增殖神经胶质瘤细胞，用抗疱疹药物更昔洛韦治疗大鼠。更昔洛韦和载体治疗的大鼠中的胶质瘤在宏观和微观上完全消退。这项技术利用了以前被认为是逆转录病毒载体的一个缺点，即它们不能将基因转移到非分裂细胞中。相反，逆转录病毒的这一特性被用来将基因传递到分裂的肿瘤细胞，而不影响非分裂的神经组织。
Direct in situ introduction of exogenous genes into proliferating tumors could provide an effective therapeutic approach for treatment of localized tumors. Rats with a cerebral glioma were given an intratumoral stereotaxic injection of murine fibroblasts that were producing a retroviral vector in which the herpes simplex thymidine kinase (HS-tk) gene had been inserted. After 5 days during which the HS-tk retroviral vectors that were produced in situ transduced the neighboring proliferating glioma cells, the rats were treated with the anti-herpes drug ganciclovir. Gliomas in the ganciclovir- and vector-treated rats regressed completely both macroscopically and microscopically. This technique exploits what was previously considered to be a disadvantage of retroviral vectors-that is, their inability to transfer genes into nondividing cells. Instead, this feature of retroviruses is used to target gene delivery to dividing tumor cells and to spare nondividing neural tissue.