R. Zufferey et al., Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors, J VIROLOGY, 73(4), 1999, pp. 2886-2892
The expression of genes delivered by retroviral vectors is often inefficien
t, a potential obstacle for their widespread use in human gene therapy. Her
e, we explored the possibility that the posttranscriptional regulatory elem
ent of woodchuck hepatitis virus (WPRE) might help resolve this problem. In
sertion of the WPRE in the 3' untranslated region of coding sequences carri
ed by either oncoretroviral or lentiviral vectors substantially increased t
heir levels of expression in a transgene-, promoter- and vector-independent
manner. The WPRE thus increased either luciferase or green fluorescent pro
tein production five- to eightfold, and effects of a comparable magnitude w
ere observed with either the immediate-early cytomegalovirus or the herpesv
irus thymidine kinase promoter and with both human immunodeficiency virus-
and murine leukemia virus-based vectors. The WPRE exerted this: influence o
nly when placed in the sense orientation, consistent with its predicted pos
ttranscriptional mechanism of action. These results demonstrate that the WP
RE: significantly improves the performance of retroviral vectors and emphas
ize that posttranscriptional regulation of gene expression should be taken
into account in the design of gene delivery systems.