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Targeted transgene expression in rat brain using lentiviral vectors
Author(s) -
Jakobsson Johan,
Ericson Cecilia,
Jansson Maria,
Björk Elin,
Lundberg Cecilia
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10719
Subject(s) - transgene , glial cell line derived neurotrophic factor , biology , viral vector , transduction (biophysics) , vesicular stomatitis virus , neurotrophic factors , microbiology and biotechnology , glial fibrillary acidic protein , genetic enhancement , cell culture , gene delivery , gene , recombinant dna , genetics , immunology , receptor , biochemistry , immunohistochemistry
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/β‐actin promoter (CAG) and the promoter for human elongation factor 1α (EF1α). 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. © 2003 Wiley‐Liss, Inc.