title: The use of an optimized chimeric envelope glycoprotein enhances the efficiency of retrograde gene transfer of a pseudotyped lentiviral vector in the primate brain.
abstract: Lentiviral vectors have been used not only for various basic research experiments, but also for a wide range of gene therapy trials in animal models. The development of a pseudotyped lentiviral vector with the property of retrograde infection allows us to introduce foreign genes into neurons that are localized in regions innervating the site of vector injection. Here, we report the efficiency of retrograde gene transfer of a recently developed FuG-E pseudotyped lentiviral vector in the primate brain by comparing its transduction pattern with that of the parental FuG-C pseudotyped vector. After injection of the FuG-E vector encoding green fluorescent protein (GFP) into the striatum of macaque monkeys, many GFP-immunoreactive neurons were found in regions projecting to the striatum, such as the cerebral cortex, thalamus, and substantia nigra. Quantitative analysis revealed that in all regions, the number of neurons retrogradely transduced with the FuG-E vector was larger than in the FuG-C vector injection case. It was also confirmed that the FuG-E vector displayed explicit neuronal specificity to the same extent as the FuG-C vector. This vector might promote approaches to pathway-selective gene manipulation and provide a powerful tool for effective gene therapy trials against neurological disorders through enhanced retrograde delivery.
authors.affiliation: Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
authors.forename: Soshi
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan. Electronic address: inoue.kenichi.6z@kyoto-u.ac.jp.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Inoue
authors.affiliation: Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Tsuge
authors.affiliation: Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Uezono
authors.affiliation: Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nagaya
authors.affiliation: Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan. Electronic address: takada.masahiko.7x@kyoto-u.ac.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takada
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics*; D008251:Macaca; D008297:Male; D009474:Neurons / Q000502:physiology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D014760:Viral Fusion Proteins
keywords: Lentivirus; Neuron; Nonhuman primates; Retrograde transport; Striatum; Viral vector