The woodchuck hepatitis virus post-transcriptional regulatory element reduces readthrough transcription from retroviral vectors View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-09

AUTHORS

T Higashimoto, F Urbinati, A Perumbeti, G Jiang, A Zarzuela, L-J Chang, D B Kohn, P Malik

ABSTRACT

The woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) increases transgene expression from a variety of viral vectors, although the precise mechanism is not known. WPRE is most effective when placed downstream of the transgene, proximal to the polyadenylation signal. We hypothesized that WPRE likely reduces viral mRNA readthrough transcription by improving transcript termination, which in turn would increase viral titers and expression. Using a Cre-lox-mediated plasmid-based assay, we found significant readthrough transcription from gamma-retroviral vector (RV) long terminal repeat (wt RV-LTR) and RV LTR with a self-inactivating deletion (SIN RV-LTR). WPRE, when placed upstream of the RV LTRs, significantly reduced readthrough transcription. Readthrough, present at much lower levels with the SIN HIV-1 LV-LTR, was also reduced with WPRE. When placed in RV vectors, WPRE increased total RV genomic mRNA; and increased viral titers from transiently transfected 293T cells and stable PG13 producer cells by 7- to 15-fold. The mechanism of increased titers and expression was not due to increased nuclear mRNA export, increased rate of viral transcription or a significant increase in viral mRNA half-life. Our results showed that WPRE improved vector genomic transcript termination to increase titers and expression from RVs. More... »

PAGES

3302979

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gt.3302979

DOI

http://dx.doi.org/10.1038/sj.gt.3302979

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003663454

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17597793


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