Targeted transgene expression in rat brain using lentiviral vectors.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/118016
- author
- Jakobsson, Johan LU ; Ericson, Cecilia LU ; Bentz, Maria LU ; Björk, Elin and Lundberg, Cecilia LU
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Neuroscience Research
- volume
- 73
- issue
- 6
- pages
- 876 - 885
- publisher
- John Wiley & Sons Inc.
- 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
- 2016-04-01 16:57:58
- date last changed
- 2022-01-28 23:22:57
@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 Inc.}}, series = {{Journal of Neuroscience Research}}, title = {{Targeted transgene expression in rat brain using lentiviral vectors.}}, url = {{http://dx.doi.org/10.1002/jnr.10719}}, doi = {{10.1002/jnr.10719}}, volume = {{73}}, year = {{2003}}, }