大量的临床前和临床研究结果已表明基因治疗是理想的疾病治疗手段,然而如何实现治疗基因表达的精确调控仍然是研究人员面临的主要挑战。目前临床前研究常用的基因调控系统多基于控制转录,对反式转录激活因子和专门启动子元件的依赖限制了该系统的临床应用。最近,仅采用RNA元件构建的几种基因表达调控系统得到开发,其作用机制为核酶介导的RNA自我切割、RNA干扰、mRNA翻译启动或终止控制等。该类系统的调控活性由小分子配体反式控制,诱导基因表达的变化幅度可观,反应快速,在哺乳动物体内外均可实现。该系统结构模块化,调控活性可调节,可以克服现有转录调节系统的一些应用局限,对将来基因治疗的临床应用具有重要意义。
Numerous preclinical and clinical studies have demonstrated the promising efficacy of gene therapy. However, precise regulation of therapeutic gene expression in vivo is still a challenge. Most of the gene regulation systems commonly used now are based on the control of transcription, but their clinical applications are limited because of their reliance on chimeric transcriptional transactivators and specialized promoter elements. More recently, several RNA-only strategies that control gene expression in mammalian cells and mice through RNA self-cleavage, RNA interference, modulation of mRNA translation initiation or termination, etc, and whose activity can be regulated by a small molecular ligand, have been developed. The extent of gene expression induction is substantial, the induction is rapid, and the expression regulation can be achieved both in vitro and in vivo. Those modular, tunable systems may overcome some of the limitations of transcription-based gene regulation systems. So they should have important clinical application in the setting of gene therapy protocols