title: Efficient gene transfer via retrograde transport in rodent and primate brains using a human immunodeficiency virus type 1-based vector pseudotyped with rabies virus glycoprotein.
abstract: The primate lentiviral vector system based on human immunodeficiency virus type 1 (HIV-1) has been used for a wide range of gene therapy trials in animal models. Axonal transport in the retrograde direction, which is observed with some viral vectors, confers a considerable advantage to gene transfer into neuronal cell bodies that are localized in regions remote from the injection site of the vectors. However, retrograde axonal transport of the HIV-1-based lentiviral vector pseudotyped with vesicular stomatitis virus glycoprotein is reported to be inefficient. In the present study, we developed an efficient gene transfer system through retrograde transport in the brain with the HIV-1-based vector pseudotyped with rabies virus glycoprotein (RV-G). Injection of the RV-G-pseudotyped HIV-1 vector into the dorsal striatum of mice yielded an increase in gene transfer into neuronal populations in the cerebral cortex, thalamus, and ventral midbrain, each of which innervates the striatum. In addition, injection of the RV-G-pseudotyped vector into the monkey striatum (putamen) resulted in highly efficient transfer into neurons in the ventral midbrain (nigrostriatal dopamine neurons). Our results indicate that pseudotyping of the HIV-1 vector with RV-G enhances the efficiency of gene transfer through retrograde axonal transport in both mouse and monkey brains. This primate lentiviral vector system will provide a powerful approach to gene therapy for neurological and neurodegenerative diseases by means of enhanced retrograde transport.
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 9601295, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kato
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Kenta
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yasoshima
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Miyachi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Hideki
authors.initials: H
authors.lastname: Hanawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takada
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics*; D001370:Axonal Transport / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism / Q000821:virology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008810:Mice, Inbred C57BL; D011323:Primates; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus