Evidence for disease-regulated transgene expression in the brain with use of lentiviral vectors.
In this study we have developed and validated a novel approach of transgene regulation in the brain. By using lentiviral vectors that incorporate promoters of genes that are up-regulated during different pathological states, we were able to regulate transgene expression in accordance with the disease process. When using a glial fibrillary acidic protein promoter, efficient disease regulation in glial cells was achieved after an excitotoxic lesion or a 6-hydroxydopamine (6-OHDA) lesion. Transgene expression was physiologically regulated and displayed a dose-dependent increase depending on the severity of lesion. Efficient regulation was also achieved in neurons when using a preproenkephlin promoter in 6-OHDA-lesioned rats, allowing combined regulation and targeting. This disease-regulated approach allows control of transgene expression in the brain without the use of inducer molecules and without overexpression of transactivator proteins.
Jakobsson
Johan
J
Department of Experimental Medical Research, Section for Neuroscience, Wallenberg Neuroscience Centre, Lund University, Lund, Sweden.
Rosenqvist
Nina
N
Mårild
Karl
K
V Agoston
Denes
D
Lundberg
Cecilia
C