| 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
|
| リソース情報 |
| ニホンザル |
|
