Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany.
Curr Opin Genet Dev. 2018 Oct;52:100-108. doi: 10.1016/j.gde.2018.06.003. Epub 2018 Oct 12.
Widespread treatment of human diseases with gene therapies necessitates the development of gene transfer vectors that integrate genetic information effectively, safely and economically. Indeed, significant efforts have been devoted to engineer novel tools that (i) achieve high-level stable gene transfer at low toxicity to the host cell; (ii) induce low levels of genotoxicity and possess a `safe' integration profile with a high proportion of integrations into safe genomic locations; and (iii) are associated with acceptable cost per treatment, and scalable/exportable vector production to serve large numbers of patients. Two decades after the discovery of the Sleeping Beauty (SB) transposon, it has been transformed into a vector system that is fulfilling these requirements. Here we review recent developments in vectorization of SB as a tool for gene therapy, and highlight clinical development of the SB system towards hematopoietic stem cell gene therapy and cancer immunotherapy.
广泛地将基因疗法用于人类疾病的治疗需要开发能够有效地、安全地、经济地将遗传信息整合入细胞的基因转移载体。事实上，已经投入了大量的努力来设计新型工具，这些工具 (i) 能够在低毒性的情况下实现高水平的稳定基因转移；(ii) 诱导低水平的遗传毒性，并具有安全的整合谱，整合入安全基因组位置的比例高；以及 (iii) 与每例治疗的可接受成本相关，并且可扩展/可出口的载体生产可满足大量患者的需求。在发现睡眠美人 (SB) 转座子的二十年后，它已经被转化为一种满足这些要求的载体系统。在这里，我们回顾了 SB 作为基因治疗工具的载体化的最新进展，并强调了 SB 系统在造血干细胞基因治疗和癌症免疫治疗方面的临床发展。
