Division of Gene Therapy & Regenerative Medicine,, Faculty of Medicine & Pharmacy, University Medical Center-Jette, Free University of Brussels, Laarbeeklaan 103, Brussels, Belgium.
Curr Gene Ther. 2011 Oct;11(5):406-13. doi: 10.2174/156652311797415836.
Transposon technology is a particularly attractive non-viral gene delivery paradigm that allows for efficient genomic integration into a variety of different cell types. In particular, transposon-mediated gene transfer is a promising tool for stem cell research, by virtue of its ability to efficiently and stably transfer genes into adult and induced pluripotent stem (iPS) cells. Moreover, transposons open up new perspectives for non-viral-mediated stem cell-based gene therapy. Several transposon systems, especially the Sleeping Beauty (SB), the piggyBac (PB) and Tol2, have been optimized for gene transfer into mammalian cells. In particular, SB resulted in stable gene transfer into various adult stem cells including human CD34(+) hematopoietic stem cells (HSCs), myoblasts and mesenchymal stem cells (MSCs). This has been confirmed with PB, yielding stable gene transfer in human CD34(+) HSCs. Recently, PB transposons were used to deliver the genes encoding the reprogramming factors into somatic cells making it an attractive technology for generating iPS cells. Subsequent de novo expression of the PB transposase resulted in traceless excision of the reprogramming cassette. This prevented inadvertent re-expression of the reprogramming factors obviating some of the concerns associated with the use of integrating vectors. Transposons have also been used as a novel non-viral paradigm to coax differentiation of iPS cells into their desired target cells by forced expression of specific differentiation factors. This review focuses on the emerging potential of transposons for gene transfer into stem cells and its implications for gene therapy and regenerative medicine.
转座子技术是一种特别有吸引力的非病毒基因传递范例，可将基因高效整合到各种不同的细胞类型中。特别是，转座子介导的基因转移是干细胞研究的一种很有前途的工具，因为它能够高效稳定地将基因转染到成体和诱导多能干细胞（iPS 细胞）中。此外，转座子为非病毒介导的基于干细胞的基因治疗开辟了新的视角。几种转座子系统，特别是睡眠美人（SB）、猪 bac（PB）和 Tol2，已经被优化用于基因转移到哺乳动物细胞中。特别是 SB 导致稳定的基因转移到各种成体干细胞中，包括人 CD34(+)造血干细胞（HSCs）、成肌细胞和间充质干细胞（MSCs）。这一点已经通过 PB 得到了证实，它在人 CD34(+) HSCs 中产生了稳定的基因转移。最近，PB 转座子被用于将编码重编程因子的基因导入体细胞，使其成为生成 iPS 细胞的一种有吸引力的技术。随后 PB 转座酶的从头表达导致重编程盒的无痕切除。这防止了重编程因子的意外重新表达，避免了与使用整合载体相关的一些问题。转座子也被用作一种新的非病毒范例，通过强制表达特定的分化因子来诱导体细胞 iPS 分化为所需的靶细胞。本文综述了转座子在将基因转移到干细胞中的新出现的潜力，及其对基因治疗和再生医学的影响。
