ArticleGene therapy2007
The woodchuck hepatitis virus post-transcriptional regulatory element reduces readthrough transcription from retroviral vectors.
Article in Gene therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- The Post-Transcriptional Regulatory Element of Hepatitis B Virus: From Discovery to Therapy.Viruses · 2024Pooled it
- Neuron-specific WWOX gene therapy produces dose-dependent, durable rescue in a model of WWOX-related epileptic encephalopathy.Molecular therapy. Advances · 2026Article
- Lentiviral-mediated expression of cytochrome P450 2D6 in HepaRG cells: new means for in vitro xenobiotic biotransformation and cellular response to chimeric viral mRNA.Archives of toxicology · 2026Article
- Structural basis of lipid-dependent allosteric gating mechanisms for PC1-PC2 ion channel.Nature communications · 2026Article
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- Laterally spreading AAV.SPR enables safe and efficient RS1 delivery to the macula after peripheral subretinal injection.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Humanized extracellular vesicles for efficient RNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- Humanized Extracellular Vesicles for Efficient RNA Delivery.bioRxiv : the preprint server for biology · 2025Article
- Lentiviral Vectors: From Wild-Type Viruses to Efficient Multi-Functional Delivery Vectors.International journal of molecular sciences · 2025Review
- Genetically encoded and modular subcellular organelle probes reveal dysfunction in lysosomes and mitochondria driven by PRKN knockout.iScience · 2025Article
- Gamma-retrovirus design for efficacious microRNA-mediated gene knock-down and protein co-expression without compromising titers.NAR molecular medicine · 2025Article
- Genetically Encoded and Modular SubCellular Organelle Probes (GEM-SCOPe) reveal lysosomal and mitochondrial dysfunction driven bybioRxiv : the preprint server for biology · 2025Article
- Current landscape of vector safety and genotoxicity after hematopoietic stem or immune cell gene therapy.Leukemia · 2025Review
- A pathological phosphorylation pattern enhances tau cooperativity on microtubules and facilitates tau filament assembly.Research square · 2025Article
- An adjusted droplet digital PCR assay for quantification of vector copy number in CAR-T cell and TCR-T cell products.Immuno-oncology technology · 2025Article
- The design of retroviral vectors used in the CAR-T products, risk management, and future perspective.MedComm · 2025Article
- Enhancing human ACE2 expression in mouse models to improve COVID-19 research.FEBS open bio · 2025Article
- Plugging synthetic DNA nanoparticles into the central dogma of life.Chemical communications (Cambridge, England) · 2024Review
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.