Recent developments in transposon-mediated gene therapy.
BACKGROUND
The continuous improvement of gene transfer technologies has broad implications for stem cell biology, gene discovery, and gene therapy. Although viral vectors are efficient gene delivery vehicles, their safety, immunogenicity and manufacturing challenges hamper clinical progress. In contrast, non-viral gene delivery systems are less immunogenic and easier to manufacture.


METHODS
In this review, we explore the emerging potential of transposons in gene and cell therapy. The safety, efficiency, and biology of novel hyperactive Sleeping Beauty (SB) and piggyBac (PB) transposon systems will be highlighted for ex vivo gene therapy in clinically relevant adult stem/progenitor cells, particularly hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), myoblasts, and induced pluripotent stem (iPS) cells. Moreover, efforts toward in vivo transposon-based gene therapy will be discussed.


CONCLUSIONS
The latest generation SB and PB transposons currently represent some of the most attractive systems for stable non-viral genetic modification of primary cells, particularly adult stem cells. This paves the way toward the use of transposons as a non-viral gene therapy approach to correct hereditary disorders including those that affect the hematopoietic system. The development of targeted integration into "safe harbor" genetic loci may further improve their safety profile.
Free University of Brussels, Division of Gene Therapy & Regenerative Medicine, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Mario
M
Di Matteo
Eyayu
E
Belay
Marinee K
MK
Chuah
Thierry
T
Vandendriessche
D002986:Clinical Trials as Topic; D004251:DNA Transposable Elements; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016662:Virus Integration
D004251:DNA Transposable Elements