title: Evidence for disease-regulated transgene expression in the brain with use of lentiviral vectors.
abstract: 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.
authors: Department of Experimental Medical Research, Section for Neuroscience, Wallenberg Neuroscience Centre, Lund University, Lund, Sweden.
authors: Johan
authors: J
authors: Jakobsson
authors: Nina
authors: N
authors: Rosenqvist
authors: Karl
authors: K
authors: Mårild
authors: Denes
authors: D
authors: V Agoston
authors: Cecilia
authors: C
authors: Lundberg