Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Gene Ther. 2017 Mar;24(3):144-150. doi: 10.1038/gt.2016.72. Epub 2016 Oct 31.
Manipulating the genetic makeup of mammalian cells using programmable nuclease-based genome-editing technology has recently evolved into a powerful avenue that holds great potential for treating genetic disorders. There are four types of genome-editing nucleases, including meganucleases, zinc finger nucleases, transcription activator-like effector nucleases and clustered, regularly interspaced, short palindromic repeat-associated nucleases such as Cas9. These nucleases have been harnessed to introduce precise and specific changes of the genome sequence at virtually any genome locus of interest. The therapeutic relevance of these genome-editing technologies, however, is challenged by the safe and efficient delivery of nuclease into targeted cells. Herein, we summarize recent advances that have been made on non-viral delivery of genome-editing nucleases. In particular, we focus on non-viral delivery of Cas9/sgRNA ribonucleoproteins for genome editing. In addition, the future direction for developing non-viral delivery of programmable nucleases for genome editing is discussed.
利用可编程核酸酶基因组编辑技术来操控哺乳动物细胞的基因结构，最近已经发展成为一种极具潜力的治疗遗传疾病的方法。基因组编辑核酸酶主要有四类，包括巨核酸酶、锌指核酸酶、转录激活因子样效应物核酸酶和规律成簇间隔短回文重复相关核酸酶，如 Cas9。这些核酸酶已经被用于在几乎任何感兴趣的基因组靶点上引入精确和特异的基因组序列变化。然而，这些基因组编辑技术的治疗相关性受到将核酸酶安全有效地递送到靶细胞的挑战。本文总结了在非病毒递送基因组编辑核酸酶方面取得的最新进展。特别关注 Cas9/sgRNA 核糖核蛋白的非病毒递送用于基因组编辑。此外，还讨论了开发可编程核酸酶非病毒递送用于基因组编辑的未来方向。
