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.