Interference with Cell-Cycle Progression by Parasitic Genetic Elements: Sleeping Beauty Joins the Club

Walisko, Oliver; Ivics, Zoltán

doi:10.4161/cc.5.12.2888

Cited by 5 publications

(5 citation statements)

References 36 publications

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“…However, it is well-known that effective plasmid DNA delivery -which is not unlikely to introduce thousands of plasmid copies per cell 39 -is directly associated with a risk of randomly inserting the DNA into the genome of treated cells, providing the cells with the capacity to stably produce transposases or nucleases. Such prolonged expression may impact cell growth, as is the case for Sleeping Beauty transposase 40,41 or perturb genome stability as seen for the PhiC31 integrase. 42,43 It is yet unclear, however, how cells are affected by sustained expression of different types of site-targeted nucleases.…”

Section: Plasmid Dna As a Source Of Genome-modifying Enzymesmentioning

confidence: 96%

Delivering the Goods for Genome Engineering and Editing

Skipper

Mikkelsen

2015

Human Gene Therapy

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A basic understanding of genome evolution and the life and impact of microorganisms, like viruses and bacteria, has been fundamental in the quest for efficient genetic therapies. The expanding tool box for genetic engineering now contains transposases, recombinases, and nucleases, all created from naturally occurring genome-modifying proteins. Whereas conventional gene therapies have sought to establish sustained expression of therapeutic genes, genomic tools are needed only in a short time window and should be delivered to cells ideally in a balanced "hit-and-run" fashion. Current state-of-the-art delivery strategies are based on intracellular production of protein from transfected plasmid DNA or in vitro-transcribed RNA, or from transduced viral templates. Here, we discuss advantages and challenges of intracellular production strategies and describe emerging approaches based on the direct delivery of protein either by transfer of recombinant protein or by lentiviral protein transduction. With focus on adapting viruses for protein delivery, we describe the concept of "all-in-one" lentiviral particles engineered to codeliver effector proteins and donor sequences for DNA transposition or homologous recombination. With optimized delivery methods-based on transferring DNA, RNA, or protein-it is no longer far-fetched that researchers in the field will indeed deliver the goods for somatic gene therapies.

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Section: Plasmid Dna As a Source Of Genome-modifying Enzymesmentioning

confidence: 96%

Delivering the Goods for Genome Engineering and Editing

Skipper

Mikkelsen

2015

Human Gene Therapy

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“…Curiously, a temporary G1 arrest enhances transposition suggesting that SB transposition might be favored in the G1 phase of the cell cycle where the NHEJ pathway of DNA repair is preferentially active (Figure 3). The SB transposase-induced G1 slowdown by interfering with cell cycle represents a common strategy shared by selfish genetic elements (Walisko & Ivics, 2006). Stable overexpression of SB has also been reported to induce a G2/M arrest and apoptosis (Galla et al, 2011).…”

Section: Modulation Of the Cell Cyclementioning

confidence: 99%

Sleeping Beautytransposition: from biology to applications

Narayanavari

Chilkunda

Ivics

et al. 2016

Critical Reviews in Biochemistry and Molecular Biology

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Sleeping Beauty (SB) is the first synthetic DNA transposon that was shown to be active in a wide variety of species. Here, we review studies from the last two decades addressing both basic biology and applications of this transposon. We discuss how host-transposon interaction modulates transposition at different steps of the transposition reaction. We also discuss how the transposon was translated for gene delivery and gene discovery purposes. We critically review the system in clinical, pre-clinical and non-clinical settings as a non-viral gene delivery tool in comparison with viral technologies. We also discuss emerging SB-based hybrid vectors aimed at combining the attractive safety features of the transposon with effective viral delivery. The success of the SBbased technology can be fundamentally attributed to being able to insert fairly randomly into genomic regions that allow stable long-term expression of the delivered transgene cassette. SB has emerged as an efficient and economical toolkit for safe and efficient gene delivery for medical applications.ARTICLE HISTORY

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“…Many authors contend that the definition of parasites includes fragments of genome identified as external to the cell in which they are found (Walisko & Ivics, 2006).…”

Section: Molecular Parasitesmentioning

confidence: 99%

“…Like viruses, they use the cell's resources to multiply. According to Walisko & Ivics (2006), just as viruses developed strategies to interact and survive in the host cell, transposons produced mechanisms capable of modulating the cell cycle to their advantage.…”

Section: Molecular Parasitesmentioning

confidence: 99%

Parasitism

Araújo¹,

Ferreira²

2014

Foundations of Paleoparasitology

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All the contents of this work, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 International license. Todo o conteúdo deste trabalho, exceto quando houver ressalva, é publicado sob a licença Creative Commons Atribição 4.0. Todo el contenido de esta obra, excepto donde se indique lo contrario, está bajo licencia de la licencia Creative Commons Reconocimento 4.0.

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Interference with Cell-Cycle Progression by Parasitic Genetic Elements: Sleeping Beauty Joins the Club

Cited by 5 publications

References 36 publications

Delivering the Goods for Genome Engineering and Editing

Delivering the Goods for Genome Engineering and Editing

Sleeping Beautytransposition: from biology to applications

Parasitism

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