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Tissue-Specific, Cell Cycle-Regulated Chimeric Transcription Factors for the Targeting of Gene Expression to Tumor Cells

Title data

Jérôme, Valérie ; Müller, Rolf:
Tissue-Specific, Cell Cycle-Regulated Chimeric Transcription Factors for the Targeting of Gene Expression to Tumor Cells.
In: Human Gene Therapy. Vol. 9 (10 December 1998) Issue 18 . - pp. 2653-2659.
ISSN 1557-7422
DOI: https://doi.org/10.1089/hum.1998.9.18-2653

Official URL: Volltext

Abstract in another language

A major challenge in the gene therapy of proliferative diseases is the specific targeting of gene expression. Here we describe a new approach based on the development of dual-specificity promoters that are both cell type specific and cell cycle regulated. The gene of interest is driven by an artificial heterodimeric transcription factor, whose DNA-binding subunit is expressed from a tissue-specific promoter, whereas the trans-activating subunit is transcribed from a cell cycle-regulated promoter. As a result gene expression occurs preferentially in the proliferating cells of a specific type of tissue. The selectivity of this strategy is demonstrated for the expression of a transgene in proliferating melanoma cells, using a combination of cyclin A and tyrosinase promoter elements. We also show that the level of expression that can be achieved by this system is sufficient to induce a clear biological effect in a TNF-alpha cytotoxicity assay.

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
Date Deposited: 26 Feb 2016 11:31
Last Modified: 20 Sep 2016 07:24
URI: https://eref.uni-bayreuth.de/id/eprint/31086