Paul Ehrlich Institute, Paul Ehrlich Strasse 51-59, D-63225 Langen, Germany.
Expert Opin Biol Ther. 2012 Feb;12(2):139-53. doi: 10.1517/14712598.2012.642358. Epub 2011 Dec 19.
Extensive efforts have been made to establish efficient and safe gene delivery protocols that could meet demanding expectations of a successful gene therapy. The Sleeping Beauty (SB) transposon system combines simplicity and inexpensive manufacture offered by plasmid-based vector formulation with integrative features exhibited by some viral vectors. Activated after over ten million years of silent genomic existence, the SB transposable element entered the 21st century as a potent technology for a broad range of applications in genome engineering, including gene therapy. Beneficially for gene therapy purposes, the SB system has been demonstrated to enable persistent expression of therapeutic genes followed by restoration of homeostasis in a variety of disease models. Importantly, this non-viral gene delivery vehicle is postulated to constitute a relatively safe vector system, because it lacks a preference for inserting into transcription units and their upstream regulatory regions, thereby minimizing genotoxic risks that might be associated with vector integration. Further evolution and wide, comprehensive preclinical testing of the SB transposon system in the context of several disease models is expected to further refine this valuable technology matched by enhanced biosafety towards disease treatment.
已经做出了广泛的努力来建立高效和安全的基因传递方案，以满足成功基因治疗的苛刻期望。睡眠美人（SB）转座子系统将基于质粒的载体配方提供的简单性和低成本制造与一些病毒载体表现出的整合特性相结合。SB 转座元件在沉默的基因组存在超过一千万年后被激活，作为基因组工程中广泛应用的强大技术进入 21 世纪，包括基因治疗。从基因治疗的角度来看，SB 系统已被证明能够在多种疾病模型中持续表达治疗基因，随后恢复体内平衡。重要的是，这种非病毒基因传递载体被认为是一种相对安全的载体系统，因为它没有插入转录单元及其上游调控区的偏好，从而最大限度地降低了与载体整合相关的遗传毒性风险。进一步的进化和在几种疾病模型中广泛、全面的 SB 转座子系统的临床前测试预计将进一步完善这项有价值的技术，并提高针对疾病治疗的生物安全性。
