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Journal of Virology, August 2003, p. 8957-8951, Vol. 77, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.16.8957-8951.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Conditional Suppression of Cellular Genes: Lentivirus Vector-Mediated Drug-Inducible RNA Interference

Maciej Wiznerowicz and Didier Trono*

Department of Genetics and Microbiology, CMU, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland

Received 27 March 2003/ Accepted 16 May 2003

RNA interference has emerged as a powerful technique to downregulate the expression of specific genes in cells and in animals, thus opening new perspectives in fields ranging from developmental genetics to molecular therapeutics. Here, we describe a method that significantly expands the potential of RNA interference by permitting the conditional suppression of genes in mammalian cells. Within a lentivirus vector background, we subjected the polymerase III promoter-dependent production of small interfering RNAs to doxycycline-controllable transcriptional repression. The resulting system can achieve the highly efficient and completely drug-inducible knockdown of cellular genes. As lentivirus vectors can stably transduce a wide variety of targets both in vitro and in vivo and can be used to generate transgenic animals, the present system should have broad applications.

* Corresponding author. Mailing address: Department of Genetics and Microbiology, CMU, Faculty of Medicine, University of Geneva, 1 rue Michel-Servet, 1211, Geneva 4, Switzerland. Phone: 41 22 702 5720. Fax: 41 22 702 5721 or 41 22 702 5702. E-mail: didier.trono{at}medecine.unige.ch.

Journal of Virology, August 2003, p. 8957-8951, Vol. 77, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.16.8957-8951.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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