Nature Methods 3, 109 - 116 (2006)
Published online: 23 January 2006; | doi:10.1038/nmeth846
A versatile tool for conditional gene expression and knockdownJolanta Szulc1, 3, Maciej Wiznerowicz1, 2, 3, Marc-Olivier Sauvain1, 2, Didier Trono1, 2, 4
& Patrick Aebischer1, 41
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. 2
"Frontiers in Genetics" National Center for Competence in Research, University of Geneva, CH-1211 Geneva, Switzerland. 3
These authors contributed equally to this work. 4
These authors contributed equally to this work.
Correspondence should be addressed to Patrick Aebischer patrick.aebischer@epfl.ch or Didier Trono didier.trono@epfl.ch Drug-inducible systems allowing the control of gene expression in mammalian cells are invaluable tools for genetic research, and could also fulfill essential roles in gene- and cell-based therapy. Currently available systems, however, often have limited in vivo functionality because of leakiness, insufficient levels of induction, lack of tissue specificity or prohibitively complicated designs. Here we describe a lentiviral vector–based, conditional gene expression system for drug-controllable expression of polymerase (Pol) II promoter-driven transgenes or Pol III promoter-controlled sequences encoding small inhibitory hairpin RNAs (shRNAs). This system has great robustness and versatility, governing tightly controlled gene expression in cell lines, in embryonic or hematopoietic stem cells, in human tumors xenotransplanted into nude mice, in the brain of rats injected intraparenchymally with the vector, and in transgenic mice generated by infection of fertilized oocytes. These results open up promising perspectives for basic or translational research and for the development of gene-based therapeutics.
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