Evidence for disease-regulated transgene expression in the brain with use of lentiviral vectors

✍ Scribed by Johan Jakobsson; Nina Rosenqvist; Karl Mårild; Denes v. Agoston; Cecilia Lundberg

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 806 KB
• Volume: 84
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20872

✦ Synopsis

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. © 2006 Wiley‐Liss, Inc.