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

开发一种新型慢病毒载体系统，用于通过逆行轴突运输研究特定神经回路标记。

• 批准号: 24650169
• 负责人: KATO Shigeki
• 金额: $ 2.08万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24650169/
• 关键词: 逆行性レンチウイルスベクター; エンベロープ; 神経回路; 逆行性遺伝子導入; レンチウイルスベクター

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.

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。

项目成果

Gene therapy

• DOI: 10.1016/b978-0-12-818422-6.00029-0
• 发表时间: 2020
• 期刊: Principles of Tissue Engineering
• 作者: S. Worgall;R. Crystal

Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice.

• DOI: 10.3389/fncir.2013.00162
• 发表时间: 2013
• 期刊: Frontiers in neural circuits
• 影响因子: 3.5
• 作者: Sooksawate T;Isa K;Matsui R;Kato S;Kinoshita M;Kobayashi K;Watanabe D;Kobayashi K;Isa T
• 通讯作者: Isa T

Highly efficient retrograde gene transfer into motor neurons by a lentiviral vector pseudotyped with fusion glycoprotein.

• DOI: 10.1371/journal.pone.0075896
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Hirano M;Kato S;Kobayashi K;Okada T;Yaginuma H;Kobayashi K
• 通讯作者: Kobayashi K

Comparative analysis for behavioral roles of the central lateral and parafascicular nuclear groups projecting to the dorsolateral striatum.

投射到背外侧纹状体的中央外侧核群和束旁核群的行为作用的比较分析。

• 作者: Shigeki KATO;Ryoji FUKABORI and Kazuto KOBAYASHI
• 通讯作者: Ryoji FUKABORI and Kazuto KOBAYASHI

Immunotoxin-mediated tract targeting in the primate brain: selective elimination of the cortico-subthalamic "hyperdirect" pathway.

• DOI: 10.1371/journal.pone.0039149
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Inoue K;Koketsu D;Kato S;Kobayashi K;Nambu A;Takada M
• 通讯作者: Takada M