Boerger A L, Snitkovsky S, Young J A
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9867-72. doi: 10.1073/pnas.96.17.9867.
Successful targeting methods represent a major hurdle to the use of retroviral vectors in cell-specific gene-delivery applications. We recently described an approach for retroviral targeting with a retroviral receptor-ligand bridge protein that was bound to the cognate cell-surface ligand receptors before viral challenge. We now report a significant improvement made to this viral targeting method by using a related bridge protein, designated TVB-EGF, comprised of the extracellular domain of the TVB receptor for subgroup B avian leukosis virus fused to epidermal growth factor (EGF). The most important activity of TVB-EGF was that it allowed specific viral entry when preloaded onto virions. Furthermore, virions preloaded with TVB-EGF were thermostable and could be produced directly from virus- packaging cells. These data suggest an approach for targeting retroviral vectors to specific cell types by using virions preloaded with a retroviral receptor-ligand bridge protein and indicate that these types of bridge proteins may be useful reagents for studying the normal mechanism of retroviral entry.
在细胞特异性基因递送应用中，成功的靶向方法是使用逆转录病毒载体的主要障碍。我们最近描述了一种用逆转录病毒受体 - 配体桥接蛋白进行逆转录病毒靶向的方法，该蛋白在病毒攻击前与同源细胞表面配体受体结合。我们现在报告对这种病毒靶向方法的一项重大改进，即使用一种相关的桥接蛋白，命名为TVB - EGF，它由与表皮生长因子（EGF）融合的B亚群禽白血病病毒TVB受体的细胞外结构域组成。TVB - EGF最重要的活性在于，当预加载到病毒粒子上时，它能使病毒特异性进入细胞。此外，预加载TVB - EGF的病毒粒子具有热稳定性，并且可以直接从病毒包装细胞中产生。这些数据表明了一种通过使用预加载有逆转录病毒受体 - 配体桥接蛋白的病毒粒子将逆转录病毒载体靶向特定细胞类型的方法，并且表明这些类型的桥接蛋白可能是研究逆转录病毒进入正常机制的有用试剂。
