Department of Stem Cell Transplant and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.
Mobile DNA, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Trends Genet. 2017 Nov;33(11):852-870. doi: 10.1016/j.tig.2017.08.008. Epub 2017 Sep 27.
The widespread clinical implementation of gene therapy requires the ability to stably integrate genetic information through gene transfer vectors in a safe, effective, and economical manner. The latest generation of Sleeping Beauty (SB) transposon vectors fulfills these requirements, and may overcome limitations associated with viral gene transfer vectors and transient nonviral gene delivery approaches that are prevalent in ongoing clinical trials. The SB system enables high-level stable gene transfer and sustained transgene expression in multiple primary human somatic cell types, thereby representing a highly attractive gene transfer strategy for clinical use. Here, we review the most important aspects of using SB for gene therapy, including vectorization as well as genomic integration features. We also illustrate the path to successful clinical implementation by highlighting the application of chimeric antigen receptor (CAR)-modified T cells in cancer immunotherapy.
基因治疗的广泛临床应用需要以安全、有效和经济的方式通过基因转移载体稳定地整合遗传信息。最新一代的睡眠美人（SB）转座子载体满足了这些要求，并可能克服与病毒基因转移载体和正在进行的临床试验中常见的瞬时非病毒基因传递方法相关的限制。SB 系统能够在多种原发性人体体细胞类型中实现高水平的稳定基因转移和持续的转基因表达，因此代表了一种非常有吸引力的临床应用基因转移策略。在这里，我们回顾了使用 SB 进行基因治疗的最重要方面，包括载体化和基因组整合特征。我们还通过突出嵌合抗原受体（CAR）修饰的 T 细胞在癌症免疫治疗中的应用来阐明成功临床应用的途径。
