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

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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

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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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(2024) · eLife · doi:10.7554/elife.91828.2.sa1
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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)
ORCID: Weitzman, Matthew D.
Hope, Thomas J.
Venue: Human Gene Therapy
Publisher: SAGE Publications
Published: 1999-09-20
Volume: 10
Issue: 14
Pages: 2295-2305
ISSN: 1043-0342 (ISSN-L)
1557-7422
DOI: 10.1089/10430349950016942
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
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
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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Enhanced Expression of Transgenes from Adeno-Associated Virus Vectors with the Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element: Implications for Gene Therapy

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