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Lesion-dependent regulation of transgene expression in the rat brain using a human glial fibrillary acidic protein-lentiviral vector.

Jakobsson, Johan LU ; Georgievska, Biljana LU ; Ericson, Cecilia LU and Lundberg, Cecilia LU (2004) In European Journal of Neuroscience 19(3). p.761-765
Abstract
The ability to regulate transgene expression will be crucial for development of gene therapy to the brain. The most commonly used systems are based on a transactivator in combination with a drug, e.g. the tetracycline-regulated system. Here we describe a different method of transgene regulation by the use of the human glial fibrillary acidic protein (GFAP) promoter. We constructed a lentiviral vector that directs transgene expression to astrocytes. Using toxin-induced lesions we investigated to what extent transgene expression could be regulated in accordance with the activation of the endogenous GFAP gene. In animals receiving excitotoxic lesions of the striatum we detected an eightfold increase of green fluorescent protein... (More)
The ability to regulate transgene expression will be crucial for development of gene therapy to the brain. The most commonly used systems are based on a transactivator in combination with a drug, e.g. the tetracycline-regulated system. Here we describe a different method of transgene regulation by the use of the human glial fibrillary acidic protein (GFAP) promoter. We constructed a lentiviral vector that directs transgene expression to astrocytes. Using toxin-induced lesions we investigated to what extent transgene expression could be regulated in accordance with the activation of the endogenous GFAP gene. In animals receiving excitotoxic lesions of the striatum we detected an eightfold increase of green fluorescent protein (GFP)-expressing cells. The vast majority of these cells did not divide, suggesting that the transgene was indeed regulated in a similar fashion as the endogenous GFAP gene. This finding will lead to the development of lentiviral vectors with autoregulatory capacities that may be very useful for gene therapy to the brain. (Less)
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@article{8d0fca64-2171-4db1-b44b-a8b6a3f921d5,
  abstract     = {The ability to regulate transgene expression will be crucial for development of gene therapy to the brain. The most commonly used systems are based on a transactivator in combination with a drug, e.g. the tetracycline-regulated system. Here we describe a different method of transgene regulation by the use of the human glial fibrillary acidic protein (GFAP) promoter. We constructed a lentiviral vector that directs transgene expression to astrocytes. Using toxin-induced lesions we investigated to what extent transgene expression could be regulated in accordance with the activation of the endogenous GFAP gene. In animals receiving excitotoxic lesions of the striatum we detected an eightfold increase of green fluorescent protein (GFP)-expressing cells. The vast majority of these cells did not divide, suggesting that the transgene was indeed regulated in a similar fashion as the endogenous GFAP gene. This finding will lead to the development of lentiviral vectors with autoregulatory capacities that may be very useful for gene therapy to the brain.},
  author       = {Jakobsson, Johan and Georgievska, Biljana and Ericson, Cecilia and Lundberg, Cecilia},
  issn         = {1460-9568},
  keyword      = {Human,Glial Fibrillary Acidic Protein: metabolism,Glial Fibrillary Acidic Protein: genetics,Genetic Vectors: metabolism,Female,Excitatory Amino Acid Agonists: toxicity,Enzyme-Linked Immunosorbent Assay,Comparative Study,Cell Count,Brain Injuries: virology,Brain Injuries: pathology,Brain Injuries: metabolism,Brain Injuries: chemically induced,Animals,Support,Sprague-Dawley,Transgenes,Non-U.S. Gov't,Gene Transfer Techniques,Gene Expression,Rats,Proliferating Cell Nuclear Antigen: genetics,Phosphopyruvate Hydratase: metabolism,Proliferating Cell Nuclear Antigen: metabolism,Luminescent Proteins: metabolism,Ibotenic Acid: toxicity,Lentivirus: genetics,Hydroxydopamines: toxicity},
  language     = {eng},
  number       = {3},
  pages        = {761--765},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Lesion-dependent regulation of transgene expression in the rat brain using a human glial fibrillary acidic protein-lentiviral vector.},
  url          = {http://dx.doi.org/10.1111/j.0953-816X.2003.03147.x},
  volume       = {19},
  year         = {2004},
}