Free University of Brussels, Division of Gene Therapy & Regenerative Medicine, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Expert Opin Biol Ther. 2012 Jul;12(7):841-58. doi: 10.1517/14712598.2012.684875.
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.
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.
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.
基因转移技术的不断改进对干细胞生物学、基因发现和基因治疗具有广泛的意义。虽然病毒载体是高效的基因传递载体，但它们的安全性、免疫原性和制造挑战阻碍了临床进展。相比之下，非病毒基因传递系统的免疫原性较低，制造也更容易。
在这篇综述中，我们探讨了转座子在基因和细胞治疗中的新兴潜力。新型超活跃 Sleeping Beauty（SB）和 piggyBac（PB）转座子系统的安全性、效率和生物学特性将被强调，用于临床相关的成人干细胞/祖细胞（尤其是造血干细胞[HSCs]、间充质干细胞[MSCs]、成肌细胞和诱导多能干细胞[iPS]细胞）的体外基因治疗。此外，还将讨论体内基于转座子的基因治疗的努力。
最新一代的 SB 和 PB 转座子目前是稳定非病毒遗传修饰原代细胞（尤其是成体干细胞）的最有吸引力的系统之一。这为转座子作为一种非病毒基因治疗方法来纠正遗传性疾病铺平了道路，包括那些影响造血系统的疾病。靶向整合到“安全港”遗传基因座的发展可能会进一步提高其安全性。
