ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Hybrid lentivirus-transposon vectors with a random integration profile in human cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 97 citations in OpenAlex.
- Reshaping the Treatment Landscape of a Galactose Metabolism Disorder.Journal of inherited metabolic disease · 2025Review
- Construction and Quantitative Evaluation of a Tissue-Specific Sleeping Beauty by EDL2-Specific Transposase Expression in Esophageal Squamous Carcinoma Cell Line KYSE-30.Molecular biotechnology · 2023Article
- Episomes and Transposases-Utilities to Maintain Transgene Expression from Nonviral Vectors.Genes · 2022Review
- Delivering genes with human immunodeficiency virus-derived vehicles: still state-of-the-art after 25 years.Journal of biomedical science · 2022Review
- Review
- Context-aware synthetic biology by controller design: Engineering the mammalian cell.Cell systems · 2021Review
- Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa-targeting guide RNA prevents wet age-related macular degeneration in mice.Nature biomedical engineering · 2021Article
- Integrase-Defective Lentiviral Vectors for Delivery of Monoclonal Antibodies against Influenza.Viruses · 2020Article
- Engineering of Primary Human B cells with CRISPR/Cas9 Targeted Nuclease.Scientific reports · 2018Article
- Preclinical and clinical advances in transposon-based gene therapy.Bioscience reports · 2017Review
- Human adipose derived mesenchymal stromal cells transduced with GFP lentiviral vectors: assessment of immunophenotype and differentiation capacity in vitro.Cytotechnology · 2016Article
- Immortalization of pig fibroblast cells by transposon-mediated ectopic expression of porcine telomerase reverse transcriptase.Cytotechnology · 2016Article
- A High-Capacity Adenoviral Hybrid Vector System Utilizing the Hyperactive Sleeping Beauty Transposase SB100X for Enhanced Integration.Molecular therapy. Nucleic acids · 2016Article
- Targeted, homology-driven gene insertion in stem cells by ZFN-loaded 'all-in-one' lentiviral vectors.eLife · 2016Article
- Towards a Safer, More Randomized Lentiviral Vector Integration Profile Exploring Artificial LEDGF Chimeras.PloS one · 2016Article
- Hybrid nonviral/viral vector systems for improved piggyBac DNA transposon in vivo delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- Human somatic cell mutagenesis creates genetically tractable sarcomas.Nature genetics · 2014Article
- Gene Therapy Used in Cancer Treatment.Biomedicines · 2014Review
- DNA transposition by protein transduction of the piggyBac transposase from lentiviral Gag precursors.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene delivery by human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors (LVs) is efficient, but genomic integration of the viral DNA is strongly biased toward transcriptionally active loci resulting in an increased risk of insertional mutagenesis in gene therapy protocols. Nonviral Sleeping Beauty (SB) transposon vectors have a significantly safer insertion profile, but efficient delivery into relevant cell/tissue types is a limitation. In an attempt to combine the favorable features of the two vector systems we established a novel hybrid vector technology based on SB transposase-mediated insertion of lentiviral DNA circles generated during transduction of target cells with integrase (IN)-defective LVs (IDLVs). By construction of a lentivirus-transposon hybrid vector allowing transposition exclusively from circular viral DNA substrates, we demonstrate that SB transposase added in trans directs efficient transposon mobilization from DNA circles in vector-transduced cells. Both transfected plasmid DNA and transduced IDLVs can serve as the source of active transposase. Most important, we demonstrate that the SB transposase overrides the natural lentiviral integration pathway and directs vector integration less frequently toward transcriptional units, resulting in a random genomic integration profile. The novel hybrid vector system combines the attractive features of efficient gene delivery by viral transduction and a safer genomic integration profile by DNA transposition.
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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.