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Targeted transgene expression in rat brain using lentiviral vectors.

Jakobsson, Johan LU ; Ericson, Cecilia LU ; Bentz, Maria LU ; Björk, Elin and Lundberg, Cecilia LU (2003) In Journal of Neuroscience Research 73(6). p.876-885
Abstract
Direct gene transfer to the adult brain is dependent on vectors that transduce non-dividing cells, such as lentiviral vectors. Another aspect of the development of gene therapy to the brain is the need for cell-specific transgene expression. Expression from vesicular stomatitis virus G-protein (VSV-G) pseudotyped lentiviral vectors has been reported to be mainly neuron specific in the brain. We constructed cell-specific lentiviral vectors using the neuron-specific enolase (rNSE) or the glial fibrillary acidic protein (hGFAP) promoters and compared them to the ubiquitous human cytomegalovirus promoter (hCMV), a hybrid CMV/-actin promoter (CAG) and the promoter for human elongation factor 1 (EF1). Our results showed that the hGFAP promoter... (More)
Direct gene transfer to the adult brain is dependent on vectors that transduce non-dividing cells, such as lentiviral vectors. Another aspect of the development of gene therapy to the brain is the need for cell-specific transgene expression. Expression from vesicular stomatitis virus G-protein (VSV-G) pseudotyped lentiviral vectors has been reported to be mainly neuron specific in the brain. We constructed cell-specific lentiviral vectors using the neuron-specific enolase (rNSE) or the glial fibrillary acidic protein (hGFAP) promoters and compared them to the ubiquitous human cytomegalovirus promoter (hCMV), a hybrid CMV/-actin promoter (CAG) and the promoter for human elongation factor 1 (EF1). Our results showed that the hGFAP promoter was expressed only in glial cells, whereas rNSE was purely neuron specific, showing that VSV-G is pantropic in the rat striatum. We conclude that the VSV-G allows transduction of both glial and neuronal cells and the promoter dictates in what cell type the transgene will be expressed. The expression of transgenes exclusively in astrocytes would allow for local delivery of secreted transgene products, such as glial cell line-derived neurotrophic factor (GDNF), circumventing the anterograde transport that may induce unwanted side effects. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Neuroscience Research
volume
73
issue
6
pages
876 - 885
publisher
John Wiley & Sons
external identifiers
  • pmid:12949915
  • wos:000185150400016
  • scopus:0041336901
ISSN
1097-4547
DOI
10.1002/jnr.10719
language
English
LU publication?
yes
id
12fa035d-79d5-46bf-b513-ff811b2fd5a8 (old id 118016)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12949915&dopt=Abstract
date added to LUP
2007-07-13 14:56:18
date last changed
2018-02-18 04:30:48
@article{12fa035d-79d5-46bf-b513-ff811b2fd5a8,
  abstract     = {Direct gene transfer to the adult brain is dependent on vectors that transduce non-dividing cells, such as lentiviral vectors. Another aspect of the development of gene therapy to the brain is the need for cell-specific transgene expression. Expression from vesicular stomatitis virus G-protein (VSV-G) pseudotyped lentiviral vectors has been reported to be mainly neuron specific in the brain. We constructed cell-specific lentiviral vectors using the neuron-specific enolase (rNSE) or the glial fibrillary acidic protein (hGFAP) promoters and compared them to the ubiquitous human cytomegalovirus promoter (hCMV), a hybrid CMV/-actin promoter (CAG) and the promoter for human elongation factor 1 (EF1). Our results showed that the hGFAP promoter was expressed only in glial cells, whereas rNSE was purely neuron specific, showing that VSV-G is pantropic in the rat striatum. We conclude that the VSV-G allows transduction of both glial and neuronal cells and the promoter dictates in what cell type the transgene will be expressed. The expression of transgenes exclusively in astrocytes would allow for local delivery of secreted transgene products, such as glial cell line-derived neurotrophic factor (GDNF), circumventing the anterograde transport that may induce unwanted side effects.},
  author       = {Jakobsson, Johan and Ericson, Cecilia and Bentz, Maria and Björk, Elin and Lundberg, Cecilia},
  issn         = {1097-4547},
  language     = {eng},
  number       = {6},
  pages        = {876--885},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Neuroscience Research},
  title        = {Targeted transgene expression in rat brain using lentiviral vectors.},
  url          = {http://dx.doi.org/10.1002/jnr.10719},
  volume       = {73},
  year         = {2003},
}