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Targeted transgene expression in rat brain using lentiviral vectors
Johan Jakobsson1, Cecilia Ericson, Maria Jansson
1Wallenberg Neuroscience Center, Department of Physiological Science, Lund University, Lund, Sweden. johan.jakobsson@mphy.lu.se
Journal of Neuroscience Research
|September 2, 2003
Summary
Lentiviral vectors with VSV-G envelopes can deliver genes to both neurons and glial cells in the brain. Specific promoters, like rNSE for neurons and hGFAP for glia, control transgene expression for targeted gene therapy.
Area of Science:
- Neuroscience
- Molecular Biology
- Gene Therapy
Background:
- Direct gene transfer to the adult brain requires vectors capable of transducing non-dividing cells, such as lentiviral vectors.
- Achieving cell-specific transgene expression is crucial for effective brain gene therapy.
Purpose of the Study:
- To construct and compare cell-specific lentiviral vectors using neuron-specific enolase (rNSE) and glial fibrillary acidic protein (hGFAP) promoters.
- To evaluate the tropism of vesicular stomatitis virus G-protein (VSV-G) pseudotyped lentiviral vectors in the rat striatum.
Main Methods:
- Construction of lentiviral vectors with rNSE, hGFAP, hCMV, CAG, and EF1 alpha promoters.
- Comparison of cell-specific transgene expression in the rat striatum.
Main Results:
- The hGFAP promoter demonstrated specific expression in glial cells.
- The rNSE promoter showed exclusive expression in neurons.
- VSV-G pseudotyped lentiviral vectors were found to be pantropic, transducing both glial and neuronal cells.
Conclusions:
- VSV-G pseudotyped lentiviral vectors can transduce both neuronal and glial cells in the brain.
- The choice of promoter determines the cell type for transgene expression.
- Targeted expression in astrocytes could enable local delivery of therapeutic proteins, potentially avoiding side effects associated with widespread transport.