title: Altering Entry Site Preference of Lentiviral Vectors into Neuronal Cells by Pseudotyping with Envelope Glycoproteins.
abstract: A lentiviral vector system provides a powerful strategy for gene therapy trials against a variety of neurological and neurodegenerative disorders. Pseudotyping of lentiviral vectors with different envelope glycoproteins not only confers the neurotropism to the vectors, but also alters the preference of sites of vector entry into neuronal cells. One major group of lentiviral vectors is a pseudotype with vesicular stomatitis virus glycoprotein (VSV-G) that enters preferentially cell body areas (somata/dendrites) of neurons and transduces them. Another group contains lentiviral vectors pseudotyped with fusion envelope glycoproteins composed of different sets of rabies virus glycoprotein and VSV-G segments that enter predominantly axon terminals of neurons and are transported through axons retrogradely to their cell bodies, resulting in enhanced retrograde gene transfer. This retrograde gene transfer takes a considerable advantage of delivering the transgene into neuronal cell bodies situated in regions distant from the injection site of the vectors. The rational use of these two vector groups characterized by different entry mechanisms will further extend the strategy for gene therapy of neurological and neurodegenerative disorders.
authors.affiliation: Section of Viral Vector Development, National Institute of Physiological Sciences, Okazaki, 444-8585, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kobayashi
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: Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, 484-8506, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, 484-8506, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takada
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan. kazuto@fmu.ac.jp.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D015316:Genetic Therapy; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D009474:Neurons / Q000821:virology*; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics*; D053586:Virus Internalization
chemical_list: D014759:Viral Envelope Proteins
keywords: Entry site; Fusion glycoprotein; Gene transfer; Lentiviral vector; Neuron; Pseudotyping; Rabies virus glycoprotein; Retrograde transport; Vesicular stomatitis virus glycoprotein