TY - JOUR
T1 - Emerging potential of transposons for gene therapy and generation of induced pluripotent stem cells.
AU - VandenDriessche, Thierry
AU - Ivics, Z.
AU - Izsvák, Z.
AU - Chuah, Marinee
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - DNA Transposable Elements/physiology
KW - Gene Therapy/adverse effects
KW - Gene Therapy/methods
KW - Gene Therapy/trends
KW - Humans
KW - Mice
KW - Models, Biological
KW - Pluripotent Stem Cells/cytology
KW - Pluripotent Stem Cells/metabolism
KW - Pluripotent Stem Cells/physiology
KW - Transcriptional Activation/physiology
KW - Animals
KW - stem cells
M3 - Article
VL - 114
SP - 1461
EP - 1468
JO - Blood
JF - Blood
SN - 0006-4971
IS - 8
ER -