Emerging potential of transposons for gene therapy and generation of induced pluripotent stem cells

Effective gene therapy requires robust delivery of the desired genes into the relevant target cells, long-term gene expression, and minimal risks of secondary effects. The development of efficient and safe nonviral vectors would greatly facilitate clinical gene therapy studies. However, nonviral gen...

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Bibliographic Details
Published in:Blood 2009-08, Vol.114 (8), p.1461-1468
Main Authors: VandenDriessche, Thierry, Ivics, Zoltán, Izsvák, Zsuzsanna, Chuah, Marinee K.L.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biotechnology
DNA Transposable Elements - physiology
Fundamental and applied biological sciences. Psychology
Gene Transfer Techniques - trends
Genetic engineering
Genetic technics
Genetic Therapy - adverse effects
Genetic Therapy - methods
Genetic Therapy - trends
Humans
Methods. Procedures. Technologies
Mice
Models, Biological
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
Pluripotent Stem Cells - physiology
Transcriptional Activation - physiology
Vectors (cloning, transfer, expression). Insertion sequences and transposons
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Summary:Effective gene therapy requires robust delivery of the desired genes into the relevant target cells, long-term gene expression, and minimal risks of secondary effects. The development of efficient and safe nonviral vectors would greatly facilitate clinical gene therapy studies. However, nonviral gene transfer approaches typically result in only limited stable gene transfer efficiencies in most primary cells. The use of nonviral gene delivery approaches in conjunction with the latest generation transposon technology based on Sleeping Beauty (SB) or piggyBac transposons may potentially overcome some of these limitations. In particular, a large-scale genetic screen in mammalian cells yielded a novel hyperactive SB transposase, resulting in robust and stable gene marking in vivo after hematopoietic reconstitution with CD34+ hematopoietic stem/progenitor cells in mouse models. Moreover, the first-in-man clinical trial has recently been approved to use redirected T cells engineered with SB for gene therapy of B-cell lymphoma. Finally, induced pluripotent stem cells could be generated after genetic reprogramming with piggyBac transposons encoding reprogramming factors. These recent developments underscore the emerging potential of transposons in gene therapy applications and induced pluripotent stem generation for regenerative medicine.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2009-04-210427