Development of a novel lentiviral vector system for the research of specific neural circuit labeling through retrograde axonal transport.

我们产生了各种类型的融合糖蛋白，其中RVG和VSVG糖蛋白片段之间的连接在RVG的近膜区域中分叉，并产生了用这些融合糖蛋白假型化的基于HIV-1的慢病毒载体。然后，我们测试了假型载体通过逆行转运进行体内基因转移的效率，将NeuRet载体与FuG-C进行比较。我们发现了一种新型的融合糖蛋白，称为E型（FuG-E），它显示出提高的逆行基因转移效率，同时保留了神经元特异性转导的性质。这种带有FuG-E的NeuRet载体将为神经系统和神经退行性疾病的遗传治疗以及各种脑功能的神经回路机制的研究提供强大的工具。

We produced various types of fusion glycoproteins, in which the junction between the RVG and VSVG glycoprotein segments diverged in the membrane-proximal region of RVG, and generated HIV-1-based lentiviral vectors pseudotyped with these fusion glycoproteins. We then tested the efficiency of the pseudotyped vectors for the in vivo gene transfer through retrograde transport, comparing that of the NeuRet vector with FuG-C. We found a novel type of fusion glycoprotein, termed type E (FuG-E), that showed improved efficiency of retrograde gene transfer while retaining the property of neuron-specific transduction. This NeuRet vector with FuG-E will provide a powerful tool for genetic treatment of neurological and neurodegenerative diseases and for the study of neural circuit mechanisms underlying various brain functions.