title: Transposon-mediated gene transfer into adult and induced pluripotent stem cells.
abstract: Transposon technology is a particularly attractive non-viral gene delivery paradigm that allows for efficient genomic integration into a variety of different cell types. In particular, transposon-mediated gene transfer is a promising tool for stem cell research, by virtue of its ability to efficiently and stably transfer genes into adult and induced pluripotent stem (iPS) cells. Moreover, transposons open up new perspectives for non-viral-mediated stem cell-based gene therapy. Several transposon systems, especially the Sleeping Beauty (SB), the piggyBac (PB) and Tol2, have been optimized for gene transfer into mammalian cells. In particular, SB resulted in stable gene transfer into various adult stem cells including human CD34(+) hematopoietic stem cells (HSCs), myoblasts and mesenchymal stem cells (MSCs). This has been confirmed with PB, yielding stable gene transfer in human CD34(+) HSCs. Recently, PB transposons were used to deliver the genes encoding the reprogramming factors into somatic cells making it an attractive technology for generating iPS cells. Subsequent de novo expression of the PB transposase resulted in traceless excision of the reprogramming cassette. This prevented inadvertent re-expression of the reprogramming factors obviating some of the concerns associated with the use of integrating vectors. Transposons have also been used as a novel non-viral paradigm to coax differentiation of iPS cells into their desired target cells by forced expression of specific differentiation factors. This review focuses on the emerging potential of transposons for gene transfer into stem cells and its implications for gene therapy and regenerative medicine.
authors.affiliation: Division of Gene Therapy & Regenerative Medicine,, Faculty of Medicine & Pharmacy, University Medical Center-Jette, Free University of Brussels, Laarbeeklaan 103, Brussels, Belgium.
authors.forename: Eyayu
authors.initials: E
authors.lastname: Belay
authors.forename: Sumitava
authors.initials: S
authors.lastname: Dastidar
authors.forename: Thierry
authors.initials: T
authors.lastname: VandenDriessche
authors.forename: Marinee K L
authors.initials: MK
authors.lastname: Chuah
mesh_terms: D004251:DNA Transposable Elements / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D019426:Integrases / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology; D019076:Transgenes; D019895:Transposases / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D019426:Integrases; D019895:Transposases; C494471:sleeping beauty transposase, human