Ohno K, Sawai K, Iijima Y, Levin B, Meruelo D
Department of Pathology, New York University Medical Center, NY 10016, USA.
Nat Biotechnol. 1997 Aug;15(8):763-7. doi: 10.1038/nbt0897-763.
Sindbis virus can infect a broad range of insect and vertebrate cell types due to the widespread distribution of the cellular receptor for the virus. The development of Sindbis virus vectors that target specific cell types could have important implications for the design of gene therapy strategies. To achieve this goal we have designed and constructed Sindbis virus particles displaying the IgG-binding domain of protein A. The protein A-envelope chimeric Sindbis virus vector has minimal infectivities against baby hamster kidney and human cell lines. When used in conjunction with monoclonal antibodies that react with cell-surface antigens, however, the protein A-envelope chimeric virus was able to infect human cell lines with high efficiency. Infection rates were 90% or higher for human lymphoblastoid cells. A variety of cells could be targeted by changing the monoclonal antibody without generating a new recombinant virus.
由于辛德毕斯病毒细胞受体的广泛分布，该病毒可感染多种昆虫和脊椎动物细胞类型。开发靶向特定细胞类型的辛德毕斯病毒载体可能对基因治疗策略的设计具有重要意义。为实现这一目标，我们设计并构建了展示蛋白A IgG结合结构域的辛德毕斯病毒颗粒。蛋白A包膜嵌合辛德毕斯病毒载体对幼仓鼠肾细胞和人细胞系的感染性极低。然而，当与与细胞表面抗原反应的单克隆抗体联合使用时，蛋白A包膜嵌合病毒能够高效感染人细胞系。人淋巴母细胞的感染率达到90%或更高。通过更换单克隆抗体可靶向多种细胞，而无需产生新的重组病毒。
