ArticlePloS one2013
Integration profile and safety of an adenovirus hybrid-vector utilizing hyperactive sleeping beauty transposase for somatic integration.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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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
26 citing papers in PubMed, 43 citations in OpenAlex.
- XPRESSO: Rapid genetic engineering of human pluripotent stem cells for durable overexpression using a modular anti-silencing vector.Stem cell reports · 2025Article
- Methodological landscape in the field of integration site identification of retroviruses and retroviral vectors.Frontiers in bioengineering and biotechnology · 2025Review
- Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024Review
- Sleeping Beauty mRNA-LNP enables stable rAAV transgene expression in mouse and NHP hepatocytes and improves vector potency.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Episomes and Transposases-Utilities to Maintain Transgene Expression from Nonviral Vectors.Genes · 2022Review
- A Novel Gene Controls a New Structure: PiggyBac Transposable Element-Derived 1, Unique to Mammals, Controls Mammal-Specific Neuronal Paraspeckles.Molecular biology and evolution · 2022Article
- Article
- Safe and efficientMolecular therapy. Methods & clinical development · 2022Article
- Adeno-Associated Virus-Based Gene Therapy for Lifelong Correction of Genetic Disease.Human gene therapy · 2020Review
- Curative in vivo hematopoietic stem cell gene therapy of murine thalassemia using large regulatory elements.JCI insight · 2020Article
- High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020Review
- RNA-guided retargeting of SeLife · 2020Article
- Adenovirus vectors in hematopoietic stem cell genome editing.FEBS letters · 2019Review
- Enhanced Tropism of Species B1 Adenoviral-Based Vectors for Primary Human Airway Epithelial Cells.Molecular therapy. Methods & clinical development · 2019Article
- In vivo hematopoietic stem cell gene therapy ameliorates murine thalassemia intermedia.The Journal of clinical investigation · 2019Article
- An Efficient In Vitro Transposition Method by a Transcriptionally Regulated Sleeping Beauty System Packaged into an Integration Defective Lentiviral Vector.Journal of visualized experiments : JoVE · 2018Article
- Preclinical and clinical advances in transposon-based gene therapy.Bioscience reports · 2017Review
- Lentivirus Mediated Correction of Artemis-Deficient Severe Combined Immunodeficiency.Human gene therapy · 2017Article
- Article
- A High-Capacity Adenoviral Hybrid Vector System Utilizing the Hyperactive Sleeping Beauty Transposase SB100X for Enhanced Integration.Molecular therapy. Nucleic acids · 2016Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB) transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR) and linear amplification-mediated PCR (LAM-PCR). Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models.
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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.