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


  • T. Vandendriessche
  • Z. Ivics
  • Z. Izsvak
  • M.K. Chuah


  • Blood


  • Blood 114 (8): 1461-1468


  • 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 non-viral vectors would greatly facilitate clinical gene therapy studies. However, non-viral gene transfer approaches typically result in only limited stable gene transfer efficiencies in most primary cells. The use of non-viral gene delivery approaches in conjunction with the latest generation transposon technology based on Sleeping Beauty (SB) or piggyBac (PB) 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 following hematopoietic reconstitution with CD34(+) hematopoietic stem/progenitor (HSC) 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 (iPS) cells could be generated following genetic reprogramming with PB transposons encoding reprogramming factors. These recent developments underscore the emerging potential of transposons in gene therapy applications and iPS generation for regenerative medicine.