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A strategy for enhancing the transcriptional activity of weak cell type-specific promoters

Title data

Nettelbeck, Dirk M. ; Jérôme, Valérie ; Müller, Rolf:
A strategy for enhancing the transcriptional activity of weak cell type-specific promoters.
In: Gene Therapy. Vol. 5 (1998) Issue 12 . - pp. 1656-1664.
ISSN 1476-5462

Official URL: Volltext

Abstract in another language

Cell type- and tissue-specific promoters play an important role in the development of site-selective vectors for gene therapy. A large number of highly specific promoters has been described, but their applicability is often hampered by their inefficient transcriptional activity. In this study, we describe a new strategy for enhancing the activity of weak promoters without loss of specificity. The basic principle of this strategy is to establish a positive feedback loop which is initiated by transcription from a cell type-specific promoter. This was achieved by using a cell type-specific promoter to drive the simultaneous expression of the desired effector/reporter gene product and a strong artificial transcriptional activator which stimulates transcription through appropriate binding sites in the promoter. Using a VP16-LexA chimeric transcription factor, we show that this approach leads to a 14- to > 100-fold enhancement of both the endothelial cell-specific von Willebrand factor promoter and the gastrointestinal-specific sucrase-isomaltase promoter while maintaining approximately 30- to > 100-fold cell type specificity.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Engineering Science
Faculties > Faculty of Engineering Science > Chair Process Biotechnology
Faculties
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 500 Natural sciences
600 Technology, medicine, applied sciences
600 Technology, medicine, applied sciences > 610 Medicine and health
Date Deposited: 26 Feb 2016 11:15
Last Modified: 26 Feb 2016 11:15
URI: https://eref.uni-bayreuth.de/id/eprint/31085