ArticleHuman gene therapy2010
Unexpectedly high copy number of random integration but low frequency of persistent expression of the Sleeping Beauty transposase after trans delivery in primary human T cells.
Article in Human gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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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
21 citing papers in PubMed.
- Engineering CAR-T cells for solid tumors: bispecific antigen targeting, tumor microenvironment modulation, and toxicity control.Immunologic research · 2025Review
- Random Insertion Reporter Gimmicks Powered by Cut-and-Paste DNA Transposons.Biomedicines · 2025Review
- Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024Review
- Chimeric antigen receptor engineered natural killer cells for cancer therapy.Experimental hematology & oncology · 2023Review
- Enhanced Biosafety of theBiomolecules · 2023Article
- NK Cells Armed with Chimeric Antigen Receptors (CAR): Roadblocks to Successful Development.Cells · 2021Review
- Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications ofInternational journal of molecular sciences · 2021Review
- A highly soluble Sleeping Beauty transposase improves control of gene insertion.Nature biotechnology · 2019Article
- Sleeping Beauty Transposon Vectors in Liver-directed Gene Delivery of LDLR and VLDLR for Gene Therapy of Familial Hypercholesterolemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Novel lentiviral vectors with mutated reverse transcriptase for mRNA delivery of TALE nucleases.Scientific reports · 2014Article
- TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer.Gene therapy · 2014Article
- DNA transposition by protein transduction of the piggyBac transposase from lentiviral Gag precursors.Nucleic acids research · 2014Article
- Sleeping beauty system to redirect T-cell specificity for human applications.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2013Article
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- Comparison of lentiviral and sleeping beauty mediated αβ T cell receptor gene transfer.PloS one · 2013Article
- β-globin matrix attachment region improves stable genomic expression of the Sleeping Beauty transposon.Journal of cellular biochemistry · 2011Article
- Ex vivo gene therapy for HIV-1 treatment.Human molecular genetics · 2011Review
- Reliable transgene-independent method for determining Sleeping Beauty transposon copy numbers.Mobile DNA · 2011Article
- Erythroid-specific expression of β-globin from Sleeping Beauty-transduced human hematopoietic progenitor cells.PloS one · 2011Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
We have shown that the Sleeping Beauty (SB) transposon system can mediate stable expression of both reporter and therapeutic genes in human primary T cells and that trans delivery (i.e., transposon and transposase are on separate plasmids) is at least 3-fold more efficient than cis delivery. One concern about trans delivery is the potential for integration of the transposase-encoding sequence into the cell genome with the possibility of continued expression, transposon remobilization, and insertional mutagenesis. To address this concern, human peripheral blood lymphocytes were nucleofected with transposase plasmid and a DsRed transposon. Eighty-eight stable DsRed(+) T cell clones were generated and found to be negative for the transposase-encoding sequence by PCR analysis of genomic DNA. Genomic PCR was positive for transposase in 5 of 15 bulk T cell populations that were similarly transfected and selected for transgene expression where copy numbers were unexpectedly high (0.007-0.047 per cell) by quantitative PCR. Transposase-positive bulk T cells lacked transposase plasmid demonstrated by Hirt (episomal) extracted DNA and showed no detectable transposase by Southern hybridization, Western blot, and quantitative RT-PCR analyses. Cytogenetic and array comparative genomic hybridization analyses of the only identified transposase-positive clone (O56; 0.867 copies per cell) showed no chromosomal abnormality or tumor formation in nude mice although transposon remobilization was detected. Our data suggest that SB delivery via plasmid in T cells should be carried out with caution because of unexpectedly high copy numbers of randomly integrated SB transposase.
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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.