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Journal of Virology, April 1999, p. 2886-2892, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances Expression of Transgenes Delivered by Retroviral Vectors

Romain Zufferey,1 John E. Donello,2 Didier Trono,1,* and Thomas J. Hope2,*

Department of Genetics and Microbiology, University of Geneva Medical School, CH-120 Geneva, Switzerland,1 and Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 920372

Received 21 September 1998/Accepted 15 December 1998

The expression of genes delivered by retroviral vectors is often inefficient, a potential obstacle for their widespread use in human gene therapy. Here, we explored the possibility that the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE) might help resolve this problem. Insertion of the WPRE in the 3' untranslated region of coding sequences carried by either oncoretroviral or lentiviral vectors substantially increased their levels of expression in a transgene-, promoter- and vector-independent manner. The WPRE thus increased either luciferase or green fluorescent protein production five- to eightfold, and effects of a comparable magnitude were observed with either the immediate-early cytomegalovirus or the herpesvirus thymidine kinase promoter and with both human immunodeficiency virus- and murine leukemia virus-based vectors. The WPRE exerted this influence only when placed in the sense orientation, consistent with its predicted posttranscriptional mechanism of action. These results demonstrate that the WPRE significantly improves the performance of retroviral vectors and emphasize that posttranscriptional regulation of gene expression should be taken into account in the design of gene delivery systems.

* Corresponding author. Mailing address for Didier Trono: Department of Genetics and Microbiology, CMU, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland. Phone: (41 22) 702 5720. Fax: (41 22) 702 5721. E-mail: didier.trono{at}medecine.unige.ch. Mailing address for Thomas J. Hope: Infectious Disease Laboratory, Salk Institute, P.O. Box 85800, San Diego, CA 92186-5800. Phone: (619) 453-4100, ext. 1559. Fax: (619) 554-0341. E-mail: hope{at}salk.edu.

Journal of Virology, April 1999, p. 2886-2892, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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