Selective transduction of malignant glioma by lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus glycoproteins
Selective transduction of malignant glioma by lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus glycoproteins
复制标题
DOI：
10.1089/1043034042431128
复制
发表时间：
2004-11-01
影响因子：
4.2
通讯作者：
Von Laer, D
中科院分区：
文献类型：
--
作者：
Miletic, H;Fischer, YH;Von Laer, D
恶性胶质瘤是最常见的原发性脑肿瘤，由于其浸润性生长，预后不良。使用病毒载体的基因疗法是传统癌症疗法的一种有吸引力的替代方案。在以前的研究中，我们建立了假型的淋巴细胞脉络丛脑膜炎病毒（LCMV）糖蛋白（GP）的慢病毒载体，并证明了人类恶性胶质瘤细胞的转导培养。在目前的方法中，我们比较了LCMV-GP-和水泡性口炎病毒糖蛋白（VSV-G）-假型慢病毒载体在体外和体内对恶性胶质瘤细胞和正常脑细胞的转导效率。LCMV-GP假型几乎完全转导星形胶质细胞，而VSV-G假型感染神经元以及星形胶质细胞。LCMV-GP假型显示出对实体胶质瘤部分的有效转导和对浸润肿瘤细胞的特异性转导。相比之下，VSV-G假型慢病毒载体仅转导实体瘤部分中的少数肿瘤细胞，并且感染浸润肿瘤区域中的大多数正常脑细胞。总之，用LCMV糖蛋白假型化的慢病毒载体代表恶性胶质瘤基因治疗的有吸引力的选择。
Malignant gliomas are the most frequent primary brain tumors and have a dismal prognosis due to their infiltrative growth. Gene therapy using viral vectors represents an attractive alternative to conventional cancer therapies. In a previous study, we established lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus (LCMV) glycoproteins (GPs) and demonstrated transduction of human malignant glioma cells in culture. In the current approach, we compared the transduction efficacy of LCMV-GP- and vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped lentiviral vectors for malignant glioma cells and normal brain cells in vitro and in vivo. LCMV-GP pseudotypes transduced almost exclusively astrocytes, whereas VSV-G pseudotypes infected neurons as well as astrocytes. LCMV-GP pseudotypes showed an efficient transduction of solid glioma parts and specific transduction of infiltrating tumor cells. In contrast, VSV-G-pseudotyped lentiviral vectors transduced only a few tumor cells in solid tumor parts and infected mostly normal brain cells in infiltrating tumor areas. In conclusion, lentiviral vectors pseudotyped with LCMV glycoproteins represent an attractive option for gene therapy of malignant glioma.