The use of an optimized chimeric envelope glycoprotein enhances the efficiency of retrograde gene transfer of a pseudotyped lentiviral vector in the primate brain
Autor: | Masahiko Takada, Soshi Tanabe, Kazuto Kobayashi, Shigeki Kato, Kiyomi Nagaya, Ken-ichi Inoue, Shiori Uezono, Maki Fujiwara, Hitomi Tsuge |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Genetic enhancement Genetic Vectors Substantia nigra Striatum Biology Macaque Green fluorescent protein Viral vector 03 medical and health sciences Transduction (genetics) 0302 clinical medicine biology.animal medicine Animals Neurons General Neuroscience Lentivirus Gene Transfer Techniques Brain General Medicine 030104 developmental biology medicine.anatomical_structure nervous system Macaca Female Neuron Neuroscience Viral Fusion Proteins 030217 neurology & neurosurgery |
Zdroj: | Neuroscience research. 120 |
ISSN: | 1872-8111 |
Popis: | 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. |
Databáze: | OpenAIRE |
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