論文 - 詳細
| RRC ID | 17525 |
|---|---|
| 著者 | Kato S, Kobayashi K, Inoue K, Kuramochi M, Okada T, Yaginuma H, Morimoto K, Shimada T, Takada M, Kobayashi K. |
| タイトル | A lentiviral strategy for highly efficient retrograde gene transfer by pseudotyping with fusion envelope glycoprotein. |
| ジャーナル | Hum Gene Ther |
| Abstract |
The lentiviral vector system based on human immunodeficiency virus type 1 (HIV-1) is used extensively in gene therapy trials of neurological and neurodegenerative diseases. Retrograde axonal transport of viral vectors offers a great advantage to the delivery of genes into neuronal cell bodies that are situated in regions distant from the injection site. Pseudotyping of HIV-1-based vectors with selective variants of rabies virus glycoprotein (RV-G) increases gene transfer via retrograde transport into the central nervous system. Because large-scale application for gene therapy trials requires high titer stocks of the vector, pseudotyping of a lentiviral vector that produces more efficient retrograde transport is needed. In the present study, we developed a novel vector system for highly efficient retrograde gene transfer by pseudotyping an HIV-1 vector with a fusion envelope glycoprotein (termed FuG-B) in which the cytoplasmic domain of RV-G was substituted by the corresponding part of vesicular stomatitis virus glycoprotein. The FuG-B pseudotype shifted the transducing property of the lentiviral vector and enhanced the retrograde transport-mediated gene transfer into different brain regions innervating the striatum with greater efficiency than that of the RV-G pseudotype in mice. In addition, injection of the FuG-B-pseudotyped vector into monkey striatum (caudate and putamen) allowed for highly efficient gene delivery into the nigrostriatal dopamine system, which is a major target for gene therapy of Parkinson's disease. Our strategy provides a powerful tool for the treatment of certain neurological and neurodegenerative diseases by promoting retrograde gene delivery via a lentiviral vector. |
| 巻・号 | 22(2) |
| ページ | 197-206 |
| 公開日 | 2011-2-1 |
| DOI | 10.1089/hum.2009.179 |
| PMID | 20954846 |
| MeSH | Animals Antigens, Viral / genetics* Corpus Striatum / metabolism Corpus Striatum / virology Genetic Therapy Genetic Vectors* Glycoproteins / genetics* HEK293 Cells HIV-1 / genetics* Humans Macaca fascicularis Mice Mice, Inbred C57BL Rabies virus / metabolism Transduction, Genetic* Viral Envelope Proteins / genetics* |
| IF | 4.51 |
| 引用数 | 83 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY MEDICINE, RESEARCH & EXPERIMENTAL GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 29 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ニホンザル | |