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  1. Article ; Online: Potent CAR-T cells engineered with Sleeping Beauty transposon vectors display a central memory phenotype.

    Ivics, Zoltán

    Gene therapy

    2020  Volume 28, Issue 1-2, Page(s) 3–5

    MeSH term(s) DNA Transposable Elements/genetics ; Genetic Vectors/genetics ; Immunotherapy, Adoptive ; Phenotype ; Receptors, Antigen, T-Cell/genetics ; T-Lymphocytes
    Chemical Substances DNA Transposable Elements ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2020-03-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 1191036-7
    ISSN 1476-5462 ; 0969-7128
    ISSN (online) 1476-5462
    ISSN 0969-7128
    DOI 10.1038/s41434-020-0138-8
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  2. Article ; Online: Sleeping Beauty

    Kovač, Adrian / Miskey, Csaba / Ivics, Zoltán

    International journal of molecular sciences

    2023  Volume 24, Issue 19

    Abstract: Transposons are nature's gene delivery vehicles that can be harnessed for experimental and therapeutic purposes. ... ...

    Abstract Transposons are nature's gene delivery vehicles that can be harnessed for experimental and therapeutic purposes. The
    MeSH term(s) Humans ; Transposases/metabolism ; DNA Transposable Elements/genetics ; Mutagenesis, Insertional ; Gene Transfer Techniques ; Transgenes
    Chemical Substances Transposases (EC 2.7.7.-) ; DNA Transposable Elements
    Language English
    Publishing date 2023-10-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241914978
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  3. Article ; Online: CRISISS: A Novel, Transcriptionally and Post-Translationally Inducible CRISPR/Cas9-Based Cellular Suicide Switch.

    Amberger, Maximilian / Grueso, Esther / Ivics, Zoltán

    International journal of molecular sciences

    2023  Volume 24, Issue 12

    Abstract: With the ever-increasing developing rate of gene and cellular therapy applications and growing accessibility due to products receiving regulatory approval, the need for effective and reliable safety mechanisms to prevent or eliminate potentially fatal ... ...

    Abstract With the ever-increasing developing rate of gene and cellular therapy applications and growing accessibility due to products receiving regulatory approval, the need for effective and reliable safety mechanisms to prevent or eliminate potentially fatal side effects is of the utmost importance. In this study, we present the CRISPR-induced suicide switch (CRISISS) as a tool to eliminate genetically modified cells in an inducible and highly efficient manner by targeting Cas9 to highly repetitive
    MeSH term(s) Animals ; Humans ; CRISPR-Cas Systems/genetics ; Gene Editing/methods ; Animals, Genetically Modified
    Language English
    Publishing date 2023-06-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24129799
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  4. Book ; Online ; Thesis: Development of transposon-mediated gene delivery systems with improved safety for the use in gene and cell therapy

    Amberger, Maximilian [Verfasser] / Marschalek, Rolf [Gutachter] / Ivics, Zoltán [Gutachter]

    2024  

    Author's details Maximilian Amberger ; Gutachter: Rolf Marschalek, Zoltán Ivics
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Universitätsbibliothek Johann Christian Senckenberg
    Publishing place Frankfurt am Main
    Document type Book ; Online ; Thesis
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  5. Article ; Online: Jumping Ahead with

    Ochmann, Matthias T / Ivics, Zoltán

    Viruses

    2021  Volume 13, Issue 1

    MeSH term(s) Animals ; DNA Transposable Elements/genetics ; Genetic Engineering ; Humans ; Recombination, Genetic ; Retroviridae/genetics ; Retroviridae/metabolism ; Structure-Activity Relationship ; Transposases/genetics ; Transposases/metabolism
    Chemical Substances DNA Transposable Elements ; Transposases (EC 2.7.7.-)
    Language English
    Publishing date 2021-01-08
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13010076
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  6. Article ; Online: CRISISS

    Maximilian Amberger / Esther Grueso / Zoltán Ivics

    International Journal of Molecular Sciences, Vol 24, Iss 9799, p

    A Novel, Transcriptionally and Post-Translationally Inducible CRISPR/Cas9-Based Cellular Suicide Switch

    2023  Volume 9799

    Abstract: With the ever-increasing developing rate of gene and cellular therapy applications and growing accessibility due to products receiving regulatory approval, the need for effective and reliable safety mechanisms to prevent or eliminate potentially fatal ... ...

    Abstract With the ever-increasing developing rate of gene and cellular therapy applications and growing accessibility due to products receiving regulatory approval, the need for effective and reliable safety mechanisms to prevent or eliminate potentially fatal side effects is of the utmost importance. In this study, we present the CRISPR-induced suicide switch (CRISISS) as a tool to eliminate genetically modified cells in an inducible and highly efficient manner by targeting Cas9 to highly repetitive Alu retrotransposons in the human genome, causing irreparable genomic fragmentation by the Cas9 nuclease and resulting cell death. The suicide switch components, including expression cassettes for a transcriptionally and post-translationally inducible Cas9 and an Alu- specific single-guide RNA, were integrated into the genome of target cells via Sleeping-Beauty- mediated transposition. The resulting transgenic cells did not show signs of any impact on overall fitness when uninduced, as unintended background expression, background DNA damage response and background cell killing were not observed. When induced, however, a strong expression of Cas9, a strong DNA damage response and a rapid halt of cell proliferation coupled with near complete cell death within four days post-induction were seen. With this proof-of-concept study, we present a novel and promising approach for a robust suicide switch with potential utility for gene and cell therapy in the future.
    Keywords suicide switch ; suicide gene ; CRISPR/Cas9 ; Alu retrotransposon ; Sleeping Beauty transposon ; gene therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Endogenous Transposase Source in Human Cells Mobilizes piggyBac Transposons.

    Ivics, Zoltán

    Molecular therapy : the journal of the American Society of Gene Therapy

    2016  Volume 24, Issue 5, Page(s) 851–854

    Language English
    Publishing date 2016-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1038/mt.2016.76
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5640: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  8. Article: A single amino acid switch converts the Sleeping Beauty transposase into an efficient unidirectional excisionase with utility in stem cell reprogramming

    Miskey, Csaba / Zuliani, Cecilia Ines / Querques, Irma / Sebe, Attila / Wang, Yongming / Izsvak, Zsuzsanna / Barabas, Orsolya / Ivics, Zoltan

    Nucleic acids research, 48(1):316-331

    2019  

    Abstract: The Sleeping Beauty (SB) transposon is an advanced tool for genetic engineering and a useful model to investigate cut-and-paste DNA transposition in vertebrate cells. Here, we identify novel SB transposase mutants that display efficient and canonical ... ...

    Institution Paul-Ehrlich-Institut
    Abstract The Sleeping Beauty (SB) transposon is an advanced tool for genetic engineering and a useful model to investigate cut-and-paste DNA transposition in vertebrate cells. Here, we identify novel SB transposase mutants that display efficient and canonical excision but practically unmeasurable genomic re-integration. Based on phylogenetic analyses, we establish compensating amino acid replacements that fully rescue the integration defect of these mutants, suggesting epistasis between these amino acid residues. We further show that the transposons excised by the exc+/int− transposase mutants form extrachromosomal circles that cannot undergo a further round of transposition, thereby representing dead-end products of the excision reaction. Finally, we demonstrate the utility of the exc+/int− transposase in cassette removal for the generation of reprogramming factor-free induced pluripotent stem cells. Lack of genomic integration and formation of transposon circles following excision is reminiscent of signal sequence removal during V(D)J recombination, and implies that cut-and-paste DNA transposition can be converted to a unidirectional process by a single amino acid change.
    Keywords Gentechnologie ; Transposon
    Language English
    Document type Article
    Database Repository for Life Sciences

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  9. Article ; Online: Self-Destruct Genetic Switch to Safeguard iPS Cells.

    Ivics, Zoltán

    Molecular therapy : the journal of the American Society of Gene Therapy

    2015  Volume 23, Issue 9, Page(s) 1417–1420

    MeSH term(s) Animals ; Caspase 9/genetics ; Gene Expression ; Genes, Transgenic, Suicide ; Genetic Therapy ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Male
    Chemical Substances Caspase 9 (EC 3.4.22.-)
    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1038/mt.2015.139
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  10. Article ; Online: Latest Advances for the Sleeping Beauty Transposon System: 23 Years of Insomnia but Prettier than Ever: Refinement and Recent Innovations of the Sleeping Beauty Transposon System Enabling Novel, Nonviral Genetic Engineering Applications.

    Amberger, Maximilian / Ivics, Zoltán

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2020  Volume 42, Issue 11, Page(s) e2000136

    Abstract: The Sleeping Beauty transposon system is a nonviral DNA transfer tool capable of efficiently mediating transposition-based, stable integration of DNA sequences of choice into eukaryotic genomes. Continuous refinements of the system, including the ... ...

    Abstract The Sleeping Beauty transposon system is a nonviral DNA transfer tool capable of efficiently mediating transposition-based, stable integration of DNA sequences of choice into eukaryotic genomes. Continuous refinements of the system, including the emergence of hyperactive transposase mutants and novel approaches in vectorology, greatly improve upon transposition efficiency rivaling viral-vector-based methods for stable gene insertion. Current developments, such as reversible transgenesis and proof-of-concept RNA-guided transposition, further expand on possible applications in the future. In addition, innate advantages such as lack of preferential integration into genes reduce insertional mutagenesis-related safety concerns while comparably low manufacturing costs enable widespread implementation. Accordingly, the system is recognized as a powerful and versatile tool for genetic engineering and is playing a central role in an ever-expanding number of gene and cell therapy clinical trials with the potential to become a key technology to meet the growing demand for advanced therapy medicinal products.
    MeSH term(s) DNA Transposable Elements ; Genetic Engineering ; Humans ; Transposases/genetics ; Transposases/metabolism
    Chemical Substances DNA Transposable Elements ; Transposases (EC 2.7.7.-)
    Language English
    Publishing date 2020-09-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202000136
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    Zs.A 2024: Show issues Location:
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