The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Enhanced Expression of Transgenes from Adeno-Associated Virus Vectors with the Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element: Implications for 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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In the citing paper
“WPRE is a 600 bp long tripartite element containing gamma, alpha, and beta elements, in the given order [16] and contributes to the strong expression of transgenes in AAV systems [11-13].”
From Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons (2014) · cites this paper as [11]
In the citing paper
“The woodchuck hepatitis post-transcriptional regulatory element (WPRE) is often included in AAV cassettes to improve viral titer and transduction efficiency via stabilizing mRNA and regulating transcriptional termination [26, 27].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [26]
Citations
Cites
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Self-citationXiao, X., Li, J., & Samulski, R. J. (1996) · Journal of Virology · doi:10.1128/jvi.70.11.8098-8108.1996 · Cited by 913
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Quantitative analysis of the packaging capacity of recombinant adeno-associated virus
Dong, J.-Y., Fan, P.-D., & Frizzell, R. A. (1996) · Human Gene Therapy · doi:10.1089/hum.1996.7.17-2101 · Cited by 583
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Self-citationFlotte, T. R., Afione, S. A., Conrad, C., McGrath, S. A., Solow, R., Oka, H., Zeitlin, P. L., Guggino, W. B., & Carter, B. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10613 · Cited by 490
Research works printed but not linked: 2
- BUCHMAN A.R., 1988, Mol. Cell. Biol., 8, 4395, 10.1128/MCB.8.10.4395 · DOI
- FLOTTE T.R., 1995, Gene Ther., 2, 357
Cited by
Sorted by citations
Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444
MacLaren, R. E., Groppe, M., Barnard, A. R., Cottriall, C. L., Tolmachova, T., Seymour, L., Clark, K. R., During, M. J., Cremers, F. P. M., Black, G. C. M., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62117-0 · Cited by 796
Thy1-GCaMP6 transgenic mice for neuronal population imaging in vivo
Dana, H., Chen, T.-W., Hu, A., Shields, B. C., Guo, C., Looger, L. L., Kim, D. S., & Svoboda, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108697 · Cited by 574
GENE THERAPY: Twenty-First Century Medicine
Verma, I. M., & Weitzman, M. D. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.050304.091637 · Cited by 630
Self-citationDemaison, C., Parsley, K. L., Brouns, G. S., Scherr, M., Battmer, K., Kinnon, C., Grez, M., & Thrasher, A. J. (2002) · Human Gene Therapy · doi:10.1089/10430340252898984 · Cited by 486
Metadata
- 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
- Publisher
- SAGE Publications
- 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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