ArticleGene therapy2009
Validation of a mutated PRE sequence allowing high and sustained transgene expression while abrogating WHV-X protein synthesis: application to the gene therapy of WAS.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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.
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Who cites it
52 citing papers in PubMed, 86 citations in OpenAlex.
- Trial
- FMR1 gene therapy restores translationally relevant phenotypes in a mouse model for fragile X syndrome.Gene therapy · 2026Article
- 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
- MiniPromoters Ple384 (TH) and Ple388 (PITX3) for targeting midbrain dopaminergic neurons in mice and monkeys.Scientific reports · 2026Article
- Novel enzymatic DNA produced from a text file achieves comparable immune responses as plasmid vaccine.NPJ vaccines · 2025Article
- Biodistribution of AAV1, AAV5, AAV9, and AAVDJ serotypes after intra-cisterna magna delivery in non-human primates.Molecular therapy. Methods & clinical development · 2025Article
- Development of VNX-101, an adeno-associated virus with less immunogenicity and efficient long-term expression of a CD19 T cell engager.Molecular therapy. Methods & clinical development · 2025Article
- Lentiviral Vectors: From Wild-Type Viruses to Efficient Multi-Functional Delivery Vectors.International journal of molecular sciences · 2025Review
- The design of retroviral vectors used in the CAR-T products, risk management, and future perspective.MedComm · 2025Article
- Enhancing lentiviral production for WAS gene therapy: a comparative analysis of stable producer cell lines evaluating flatware system and adherent bioreactors in perfusion mode.Frontiers in bioengineering and biotechnology · 2025Article
- Article
- An optimized protocol for quality control of gene therapy vectors using nanopore direct RNA sequencing.Genome research · 2024Article
- New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates.Scientific reports · 2024Article
- rAAV-PHP.B escapes the mouse eye and causes lethality whereas rAAV9 can transduce aniridic corneal limbal stem cells without lethality.Gene therapy · 2023Article
- Delivering genes with human immunodeficiency virus-derived vehicles: still state-of-the-art after 25 years.Journal of biomedical science · 2022Review
- Distribution of cardiomyocyte-selective adeno-associated virus serotype 9 vectors in swine following intracoronary and intravenous infusion.Physiological genomics · 2022Article
- Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022Review
- Transgene distribution and immune response after ultrasound delivery of rAAV9 and PHP.B to the brain in a mouse model of amyloidosis.Molecular therapy. Methods & clinical development · 2021Article
- Review
- Intracerebroventricular Administration of AAV9-PHP.B SYN1-EmGFP Induces Widespread Transgene Expression in the Mouse and Monkey Central Nervous System.Human gene therapy · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
The woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) is widely used in retroviral gene transfer vectors. However, this element contains an open-reading frame (ORF) encoding a truncated peptide of the woodchuck hepatitis virus X protein (WHX). Because we are developing a lentiviral vector for the gene therapy of Wiskott-Aldrich syndrome (WAS), we evaluated whether the WPRE was needed in the gene transfer cassette and tested the possibility of replacing it with a mutated derivative. The transcriptional activity of the WPRE was undetectable in the context of the lentiviral vector but the element was capable of translating a polypeptide. This capability was abrogated by mutating the WHX ORF translation start. The WPRE was required to express high levels of the transgene and for that, the native form or mutated derivatives functioned equivalently. The vector using a WAS gene promoter and the mut6 WPRE induced long-term expression of the WAS transgene in vivo, correcting cytoskeletal defects, thymocyte and B-cell numbers and improved the colitis of WAS-null mice. By providing additional evidence of efficacy of this WAS lentiviral vector with improved safety features, our results validate a mutated WPRE, which should be useful in future gene therapy applications.
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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.