Macrolide- and tetracycline-adjustable siRNA-mediated gene silencing in mammalian cells using polymerase II-dependent promoter derivatives

Biotechnology and Bioengineering
Laetitia Malphettes, Martin Fussenegger

Abstract

RNA interference has emerged as a powerful technology for downregulation of specific genes in cells and animals. We have pioneered macrolide- and tetracycline-adjustable short interfering RNA (siRNA) expression for conditional target gene translation fine-tuning in mammalian/human cell lines based on modified RNA polymerase II promoters. Established macrolide- and tetracycline-dependent transactivators/trans-silencers bound and activated modified target promoters tailored for optimal siRNA expression in response to clinical antibiotics' dosing regimes and modulated desired target genes in Chinese hamster ovary (CHO-K1) and human fibrosarcoma (HT-1080) cells with high precision. Further optimization of adjustable RNA polymerase II-based siRNA-specific promoters as well as their combination with various transmodulators enabled near-perfect regulation configurations in specific cell types. Devoid of major genetic constraints compared to basic RNA polymerase III-based siRNA-specific promoters, we expect RNA polymerase II counterparts to significantly advance siRNA-based molecular interventions in biopharmaceutical manufacturing and gene-function analysis as well as gene therapy and tissue engineering.

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Citations

May 21, 2013·Nucleic Acids Research·Marc FolcherMartin Fussenegger
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·T F WestbrookS J Elledge
Apr 4, 2012·Annual Review of Chemical and Biomolecular Engineering·Markus Wieland, Martin Fussenegger
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Sep 12, 2006·Metabolic Engineering·Laetitia MalphettesMartin Fussenegger
Sep 26, 2006·Metabolic Engineering·Laetitia Malphettes, Martin Fussenegger
Feb 21, 2006·Journal of Biotechnology·Laetitia Malphettes, Martin Fussenegger
May 5, 2006·Biotechnology and Bioengineering·Frederyk A NgantungDaniel I C Wang
Dec 14, 2006·Biotechnology and Bioengineering·David Greber, Martin Fussenegger
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May 21, 2005·Biotechnology Progress·Wilfried WeberMartin Fussenegger

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