Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates

@article{Mts2009MolecularEO,
  title={Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates},
  author={Lajos M{\'a}t{\'e}s and Marinee Khim Chuah and Eyayu Belay and Boris Jerchow and Namitha Manoj and Abel Acosta-Sanchez and Dawid P. Grzela and Andrea Schmitt and Katja Becker and Janka M{\'a}trai and Ling Ma and Ermira Samara-Kuko and Conny A. Gysemans and Diana Pryputniewicz and Csaba Miskey and Bradley S. Fletcher and Thierry VandenDriessche and Zolt{\'a}n Ivics and Zsuzsanna Izsv{\'a}k},
  journal={Nature Genetics},
  year={2009},
  volume={41},
  pages={753-761}
}
The Sleeping Beauty (SB) transposon is a promising technology platform for gene transfer in vertebrates; however, its efficiency of gene insertion can be a bottleneck in primary cell types. A large-scale genetic screen in mammalian cells yielded a hyperactive transposase (SB100X) with ∼100-fold enhancement in efficiency when compared to the first-generation transposase. SB100X supported 35–50% stable gene transfer in human CD34+ cells enriched in hematopoietic stem or progenitor cells… Expand
Rodent transgenesis mediated by a novel hyperactive Sleeping Beauty transposon system.
  • L. Mátés
  • Biology, Medicine
  • Methods in molecular biology
  • 2011
TLDR
A new hyperactive version (SB100X) of the vertebrate-specific Sleeping Beauty (SB) transposase, which is over 100-fold more active in mammalian cells than the prototype and opens the possibility of designing SB based transgenes also for in vivo knockdown experiments. Expand
The hyperactive Sleeping Beauty transposase SB100X improves the genetic modification of T cells to express a chimeric antigen receptor
TLDR
SB100X improves SB transposition in primary human T cells and can be titrated with an SB transposon plasmid to improve the generation of CD19-specific CAR+ T cells. Expand
A highly soluble Sleeping Beauty transposase improves control of gene insertion
TLDR
It is demonstrated that hsSB can be delivered with transposon DNA to genetically modify cell lines and embryonic, hematopoietic and induced pluripotent stem cells (iPSCs), overcoming uncontrolled transposase activity. Expand
Hyperactive sleeping beauty transposase enables persistent phenotypic correction in mice and a canine model for hemophilia B.
TLDR
It is shown that hyperactive transposase system delivered by high-capacity adenoviral vectors can result in somatic integration of a canine factor IX expression-cassette in canine liver, facilitating stabilized transgene expression and persistent haemostatic correction of canine hemophilia B with negligible toxicity. Expand
Comparative genomic integration profiling of Sleeping Beauty transposons mobilized with high efficacy from integrase-defective lentiviral vectors in primary human cells.
It has been previously shown that integrase-defective HIV-1-based gene vectors can serve, with moderate efficiency, as substrate for DNA transposition by a transiently expressed Sleeping Beauty (SB)Expand
Optimized Sleeping Beauty transposons rapidly generate stable transgenic cell lines.
TLDR
Improvements made to the existing SB vector system are reported and two new vector types for robust constitutive or inducible expression of any gene of interest are presented, available in 16 variants with different selection marker and fluorescent protein expression to fit most experimental requirements. Expand
Sleeping Beauty-Mediated Drug Resistance Gene Transfer in Human Hematopoietic Progenitor Cells.
TLDR
SB-mediated transposition of hematopoietic progenitor cells conferred resistance to methotrexate and dipyridamole, a nucleoside transport inhibitor that tightens MTX selection conditions, as assessed by in vitro hematopsic colony formation. Expand
Genomic Analysis of Sleeping Beauty Transposon Integration in Human Somatic Cells
TLDR
A side-by-side comparison of the SA and the widely used T2 arrangement of transposon vectors carrying increasing DNA cargoes, up to 18 kb, shows important features as a system for delivering large gene constructs for gene therapy applications. Expand
Comparative analysis of transposable element vector systems in human cells.
TLDR
SB was the most efficient system under conditions where the availability of the transposon DNA is limiting the transposition reaction including hard-to-transfect hematopoietic stem/progenitor cells (HSCs), and the most sensitive to OPI, underpinning the need for careful optimization of thetransposon components. Expand
Efficient Non-viral Gene Delivery into Human Hematopoietic Stem Cells by Minicircle Sleeping Beauty Transposon Vectors
The Sleeping Beauty (SB) transposon system is a non-viral gene delivery platform that combines simplicity, inexpensive manufacture, and favorable safety features in the context of human applications.Expand
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TLDR
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TLDR
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TLDR
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TLDR
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