Specific Targeting of Human IL-13 Receptor ýý2-Positive Cells with Lentiviral Vectors Displaying IL-13.
Specific Targeting of Human IL-13 Receptor ýý2-Positive Cells with Lentiviral Vectors Displaying IL-13.
复制标题
使用显示 IL-13 的慢病毒载体特异性靶向人 IL-13 受体 α2 阳性细胞。
DOI：
10.1089/hgtb.2012.054
复制
发表时间：
2012
影响因子：
--
通讯作者：
Reiser,Jakob
中科院分区：
文献类型：
--
作者：
Ou,Wu;Marino,MichaelP;Suzuki,Akiko;Joshi,BharatH;Husain,SyedR;Maisner,Andrea;Galanis,Evanthia;Puri,Raj;Reiser,Jakob
在体外和体内选择性和有效地将转基因递送到特定细胞类型的能力仍然是基因治疗中的一个艰巨挑战。慢病毒载体具有几个优点，使得它们作为基因递送载体具有吸引力，并且它们的向性可以通过假型化改变，从而允许转基因递送至特定的细胞群体。人白细胞介素-13受体α2（IL-13 R α2）在许多不同的人类肿瘤中独特地过表达，使其成为癌症治疗的有吸引力的靶点。在这项研究中，我们检查了IL-13 R α2阳性肿瘤细胞是否可以特异性靶向慢病毒载体假型，该假型含有来自麻疹病毒（MV）的截短融合（F）蛋白和C末端携带IL-13的尾部截短和受体盲性MV血凝素（H）蛋白。该慢病毒载体在体外能有效地转导高表达IL-13 R α2的细胞，而在体内则不能有效地转导低表达IL-13 R α 2的细胞，在皮下和颅内胶质瘤模型中，该慢病毒载体特异性地靶向免疫缺陷小鼠中IL-13 R α2阳性胶质瘤细胞异种移植物。可以开发类似的慢病毒载体用于靶向表达特异性细胞表面受体的其他肿瘤。
The ability to selectively and efficiently target transgene delivery to specific cell typesin vitroandin vivoremains one of the formidable challenges in gene therapy. Lentiviral vectors have several advantages that make them attractive as gene delivery vehicles and their tropism can be altered through pseudotyping, allowing transgene delivery to specific populations of cells. The human interleukin-13 receptor α2 (IL-13Rα2) is uniquely overexpressed in many different human tumors, making it an attractive target for cancer therapy. In this study, we examined whether IL-13Rα2-positive tumor cells can be specifically targeted with lentiviral vector pseudotypes containing a truncated fusion (F) protein derived from measles virus (MV) and a tail-truncated and receptor-blind MV hemagglutinin (H) protein bearing IL-13 at the C terminus. The retargeted lentiviral vector efficiently transduced cells that express high levels of IL-13Rα2, but not cells expressing low levels of IL-13Rα2in vitro.In vivo, it specifically targeted IL-13Rα2-positive glioma cell xenografts in immunodeficient mice in the context of subcutaneous and intracranial glioma models. Similar lentiviral vectors may be developed for targeting other tumors expressing specific cell surface receptors.