Cited by 279Virus-based gene therapy researchRNA Interference and Gene DeliveryRNA Research and Splicing

Enhanced Expression of Transgenes from Adeno-Associated Virus Vectors with the Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element: Implications for Gene Therapy

Loeb, Jonathan E., Cordier, Wendy S., Harris, Matthew E., Weitzman, Matthew D., Hope, Thomas J.·1999·Human Gene Therapy

Abstract

The woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) evolved to stimulate the expression of intronless viral messages. To determine whether this ability to enhance expression could be useful in nonviral and heterologous viral gene delivery systems, we analyzed the ability of the WPRE to elevate the expression of a cDNA encoding the green fluorescent protein (GFP) in these contexts. We find that the WPRE can stimulate the expression of GFP when the gene is delivered by transfection or transduction with recombinant adeno-associated virus (AAV). Enhancement occurred both during transient expression and when the gene is stably incorporated into the genome of target cells. This enhancement required that the WPRE be located in cis within the GFP message, and was observed in both transformed cell lines and primary human fibroblasts. These results demonstrate that the WPRE will be an effective tool for increasing the long-term expression of transgenes in gene therapy.

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Crossref · 10.1089/10430349950016942

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Authors
Loeb, J. E., Cordier, W. S., Harris, M. E., Weitzman, M. D., & Hope, T. J.
Affiliations
Salk Institute for Biological Studies (US)
Venue
Human Gene Therapy
Published
1999-09-20
Volume
10
Issue
14
Pages
2295-2305
ISSN
  • 1043-0342 (ISSN-L)
  • 1557-7422
OpenAlex
W2142334980
Cited by
279
References
35
Citations by year
2026: 3 · 2025: 7 · 2024: 18 · 2023: 8 · 2022: 10 · 2021: 15 · 2020: 11 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 5 · 2015: 10 · 2014: 11 · 2013: 6 · 2012: 6
FWCI
5.23
Type
journal article
Language
en
Open access
closed
Locations
  • Human Gene Therapy (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
woodchuck hepatitis virus, adeno-associated virus vectors, green fluorescent protein, gene therapy, cis-acting regulation, stable transfection, transduction, human fibroblasts, long-term transgene expression
MeSH terms
Dependovirus, Cell Line, Flow Cytometry, Genetic Vectors, Humans, Luminescent Proteins, Regulatory Sequences, Nucleic Acid, RNA Processing, Post-Transcriptional, RNA, Viral, Blotting, Western, Gene Expression Regulation, Viral, Hepatitis B Virus, Woodchuck, Gene Transfer Techniques, Transgenes, Green Fluorescent Proteins

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