Transgene expression in the guinea pig cochlea mediated by a lentivirus-derived gene transfer vector

被引:95
作者
Han, JJ
Mhatre, AN
Wareing, M
Pettis, R
Gao, WQ
Zufferey, RN
Trono, D
Lalwani, AK
机构
[1] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, Lab Mol Otol, Epstein Labs, San Francisco, CA 94143 USA
[2] Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA
[3] Univ Geneva, Sch Med, Dept Genet & Microbiol, CH-120 Geneva, Switzerland
关键词
D O I
10.1089/10430349950017545
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The utility of lentivirus as a gene delivery vector in the cochlea was evaluated in vitro and irt vivo, Lentivirus transduction was assessed through expression analysis of a reporter gene, green fluorescent protein (GFP), integrated within the viral genome, In vitro characterization of lentivirus-GFP was assessed by infection of explants from cochleas of neonatal rat. The lentiviral vector transduced both spiral ganglion neurons (SGNs) and glial cells. III vivo characterization of lentivirus-GFP was assessed by directly infusing the vector into the guinea pig cochlea via an osmotic minipump, Sections of lentivirus-infused cochlea revealed a highly restricted fluorescence pattern limited to the periphery of the perilymphatic space. Transduction of SGNs and glial cells by lentivirus in vitro but not iir vivo suggests limited dissemination of the viral vector from the perilymphatic space. The cellular and tissue architecture of the lentivirus-infused cochlea was intact and free of inflammation. Restricted transduction of cell types confined to the periphery of the perilymphatic space by the lentivirus is ideal for stable production of gene products secreted into the perilymph.
引用
收藏
页码:1867 / 1873
页数:7
相关论文
共 14 条
[1]   GREEN FLUORESCENT PROTEIN AS A MARKER FOR GENE-EXPRESSION [J].
CHALFIE, M ;
TU, Y ;
EUSKIRCHEN, G ;
WARD, WW ;
PRASHER, DC .
SCIENCE, 1994, 263 (5148) :802-805
[2]   Defective HSV-1 vector expressing BDNF in auditory ganglia elicits neurite outgrowth: Model for treatment of neuron loss following cochlear degeneration [J].
Geschwind, MD ;
Hartnick, CJ ;
Liu, W ;
Amat, J ;
VandeWater, TR ;
Federoff, HJ .
HUMAN GENE THERAPY, 1996, 7 (02) :173-182
[3]   AEQUOREA GREEN FLUORESCENT PROTEIN - EXPRESSION OF THE GENE AND FLUORESCENCE CHARACTERISTICS OF THE RECOMBINANT PROTEIN [J].
INOUYE, S ;
TSUJI, FI .
FEBS LETTERS, 1994, 341 (2-3) :277-280
[4]   Green fluorescent protein as a reporter for gene transfer studies in the cochlea [J].
Lalwani, AK ;
Han, JJ ;
Walsh, BJ ;
Zolotukhin, S ;
Muzyczka, N ;
Mhatre, AN .
HEARING RESEARCH, 1997, 114 (1-2) :139-147
[5]  
Lalwani AK, 1996, GENE THER, V3, P588
[6]   Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector [J].
Naldini, L ;
Blomer, U ;
Gage, FH ;
Trono, D ;
Verma, IM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (21) :11382-11388
[7]   In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector [J].
Naldini, L ;
Blomer, U ;
Gallay, P ;
Ory, D ;
Mulligan, R ;
Gage, FH ;
Verma, IM ;
Trono, D .
SCIENCE, 1996, 272 (5259) :263-267
[8]   Adenoviral-mediated gene transfer into guinea pig cochlear cells in vivo [J].
Raphael, Y ;
Frisancho, JC ;
Roessler, BJ .
NEUROSCIENCE LETTERS, 1996, 207 (02) :137-141
[9]  
Smith KT, 1996, GENE THER, V3, P190
[10]  
ZHENG JL, 1995, J NEUROSCI, V15, P5079