Tissue-specific, cell cycle-regulated chimeric transcription factors for the targeting of gene expression to tumor cells

Citation
V. Jerome et R. Muller, Tissue-specific, cell cycle-regulated chimeric transcription factors for the targeting of gene expression to tumor cells, HUM GENE TH, 9(18), 1998, pp. 2653-2659
Citations number
21
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENE THERAPY
ISSN journal
10430342 → ACNP
Volume
9
Issue
18
Year of publication
1998
Pages
2653 - 2659
Database
ISI
SICI code
1043-0342(199812)9:18<2653:TCCCTF>2.0.ZU;2-L
Abstract
A major challenge in the gene therapy of proliferative diseases is the spec ific targeting of gene expression. Here we describe a new approach based on the development of dual-specificity promoters that are both cell type spec ific and cell cycle regulated. The gene of interest is driven by an artific ial heterodimeric transcription factor, whose DNA-binding subunit is expres sed from a tissue-specific promoter, whereas the transactivating subunit is transcribed from a cell cycle-regulated promoter, As a result gene express ion 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 cyc lin A and tyrosinase promoter elements. We also show that the level of expr ession that can be achieved by this system is sufficient to induce a clear biological effect in a TNF-alpha cytotoxicity assay.