ArticleNucleic acids research2011
Avoiding cytotoxicity of transposases by dose-controlled mRNA delivery.
Article in Nucleic acids research, 2011. 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 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
35 citing papers in PubMed, 59 citations in OpenAlex.
- Random Insertion Reporter Gimmicks Powered by Cut-and-Paste DNA Transposons.Biomedicines · 2025Review
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- 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
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- Novel suspension retroviral packaging cells generated by transposition using transposase encoding mRNA advance vector yields and enable production in bioreactors.Frontiers in bioengineering and biotechnology · 2023Article
- Molecular and Functional Characterization of BDNF-Overexpressing Human Retinal Pigment Epithelial Cells Established byInternational journal of molecular sciences · 2022Article
- Improved alpharetrovirus-based Gag.MS2 particles for efficient and transient delivery of CRISPR-Cas9 into target cells.Molecular therapy. Nucleic acids · 2022Article
- The Past, Present, and Future of Non-Viral CAR T Cells.Frontiers in immunology · 2022Review
- Two cases of T cell lymphoma following Piggybac-mediated CAR T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications ofInternational journal of molecular sciences · 2021Review
- A novel all-in-one conditional knockout system uncovered an essential role of DDX1 in ribosomal RNA processing.Nucleic acids research · 2021Article
- Potential of transposon-mediated cellular reprogramming towards cell-based therapies.World journal of stem cells · 2020Review
- A highly soluble Sleeping Beauty transposase improves control of gene insertion.Nature biotechnology · 2019Article
- Transient Retrovirus-Based CRISPR/Cas9 All-in-One Particles for Efficient, Targeted Gene Knockout.Molecular therapy. Nucleic acids · 2018Article
- 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
- Transposon-mediated Generation of Cellular and Mouse Models of Splicing Mutations to Assess the Efficacy of snRNA-based Therapeutics.Molecular therapy. Nucleic acids · 2016Article
- Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives.Journal of translational medicine · 2016Review
- Viral and Synthetic RNA Vector Technologies and Applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- 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
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Sleeping Beauty (SB) transposase and its newly developed hyperactive variant, SB100X, are of increasing interest for genome modification in experimental models and gene therapy. The potential cytotoxicity of transposases requires careful assessment, considering that residual integration events of transposase expression vectors delivered by physicochemical transfection or episomal retroviral vectors may lead to permanent transposase expression and resulting uncontrollable transposition. Comparing retrovirus-based approaches for delivery of mRNA, episomal DNA or integrating DNA, we found that conventional SB transposase, SB100X and a newly developed codon-optimized SB100Xo may trigger premitotic arrest and apoptosis. Cell stress induced by continued SB overexpression was self-limiting due to the induction of cell death, which occurred even in the absence of a co-transfected transposable element. The cytotoxic effects of SB transposase were strictly dose dependent and heralded by induction of p53 and c-Jun. Inactivating mutations in SB's catalytic domain could not abrogate cytotoxicity, suggesting a mechanism independent of DNA cleavage activity. An improved approach of retrovirus particle-mediated mRNA transfer allowed transient and dose-controlled expression of SB100X, supported efficient transposition and prevented cytotoxicity. Transposase-mediated gene transfer can thus be tuned to maintain high efficiency in the absence of overt cell damage.
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What OpenQuestion holds
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.