Sawai K, Meruelo D
Department of Pathology and Kaplan Cancer Center, New York University Medical Center, 550 First Avenue, New York, New York, 10016, USA.
Biochem Biophys Res Commun. 1998 Jul 20;248(2):315-23. doi: 10.1006/bbrc.1998.8922.
The development of Sindbis virus vectors that can target specific cell types would provide an important gene therapy strategy. We explored the possibility of designing a Sindbis virus vector that can target human choriocarcinoma cells via ligand-receptor interaction. The Sindbis virus envelope gene was modified by insertion of the alpha- and beta-hCG genes. The chimeric helper RNA was then transfected into BHK cells along with a virus-based expression vector, allowing the production of virus particles containing hCG-envelope chimeras. The hCG-envelope chimeric virus vector has minimal infectivities against BHK cells and human cancer cells which do not contain LH/CG receptors on their surface. This vector can, however, infect and transfer a reporter gene to choriocarcinoma cells as well as other cells bearing LH/CG receptors. This chimeric Sindbis virus vector may provide a novel approach for gene therapy of gestational trophoblast disease and placental dysfunction.
能够靶向特定细胞类型的辛德毕斯病毒载体的开发将提供一种重要的基因治疗策略。我们探索了设计一种能通过配体-受体相互作用靶向人绒毛膜癌细胞的辛德毕斯病毒载体的可能性。通过插入α和β人绒毛膜促性腺激素基因对辛德毕斯病毒包膜基因进行修饰。然后将嵌合辅助RNA与基于病毒的表达载体一起转染到BHK细胞中，从而产生含有hCG包膜嵌合体的病毒颗粒。hCG包膜嵌合病毒载体对表面不含有促黄体生成素/绒毛膜促性腺激素受体的BHK细胞和人类癌细胞的感染性极低。然而，这种载体能够感染并将报告基因转移至绒毛膜癌细胞以及其他带有促黄体生成素/绒毛膜促性腺激素受体的细胞。这种嵌合辛德毕斯病毒载体可能为妊娠滋养细胞疾病和胎盘功能障碍的基因治疗提供一种新方法。
