Novel promoter/transactivator configurations for macrolide- and streptogramin-responsive transgene expression in mammalian cells

Background The recently developed heterologous macrolide‐ (E.REX system) and streptogramin‐ (PIP system) responsive gene regulation systems show significant differences in their regulation performance in diverse cell lines. Methods In order to provide optimal regulation modalities for a wide variety...

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Bibliographic Details
Published in:The journal of gene medicine 2002-11, Vol.4 (6), p.676-686
Main Authors: Weber, Wilfried, Kramer, Beat P., Fux, Cornelia, Keller, Bettina, Fussenegger, Martin
Format: Article
Language:English
Subjects:
Animals
Base Sequence
CHO Cells
Cricetinae
DNA Primers
E.REX
erythromycin
gene regulation system
Gene therapy
Humans
K562 Cells
Macrolides - pharmacology
Pip system
pristinamycin
Promoter Regions, Genetic
Streptogramins - pharmacology
Tetracyclines - pharmacology
tissue engineering
Trans-Activators - metabolism
Transgenes
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Summary:Background The recently developed heterologous macrolide‐ (E.REX system) and streptogramin‐ (PIP system) responsive gene regulation systems show significant differences in their regulation performance in diverse cell lines. Methods In order to provide optimal regulation modalities for a wide variety of mammalian cell lines, we have performed a detailed analysis of E.REX and PIP systems modified in (i) the transactivation domains of the antibiotic‐dependent transactivators, (ii) the type of minimal promoter used, and (iii) the spacing between the operator module and the minimal promoter. Results These novel E.REX and PIP regulation components showed not only dramatically improved regulation performance in some cell types, but also enabled their use in cell lines which had previously been inaccessible to regulated transgene expression. Conclusions Due to their modular set‐up the novel E.REX and PIP regulation systems presented here are most versatile and ready for future upgrades using different cell‐specific key regulation components. Copyright © 2002 John Wiley & Sons, Ltd.
ISSN:1099-498X
1521-2254
DOI:10.1002/jgm.314