Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
Cells. 2020 Apr 13;9(4):953. doi: 10.3390/cells9040953.
Gene editing permits changing specific DNA sequences within the vast genomes of human cells. Stem cells are particularly attractive targets for gene editing interventions as their self-renewal and differentiation capabilities consent studying cellular differentiation processes, screening small-molecule drugs, modeling human disorders, and testing regenerative medicines. To integrate gene editing and stem cell technologies, there is a critical need for achieving efficient delivery of the necessary molecular tools in the form of programmable DNA-targeting enzymes and/or exogenous nucleic acid templates. Moreover, the impact that the delivery agents themselves have on the performance and precision of gene editing procedures is yet another critical parameter to consider. Viral vectors consisting of recombinant replication-defective viruses are under intense investigation for bringing about efficient gene-editing tool delivery and precise gene-editing in human cells. In this review, we focus on the growing role that adenoviral vectors are playing in the targeted genetic manipulation of human stem cells, progenitor cells, and their differentiated progenies in the context of in vitro and ex vivo protocols. As preamble, we provide an overview on the main gene editing principles and adenoviral vector platforms and end by discussing the possibilities ahead resulting from leveraging adenoviral vector, gene editing, and stem cell technologies.
基因编辑允许改变人类细胞庞大基因组内的特定 DNA 序列。干细胞是基因编辑干预的特别有吸引力的目标,因为它们的自我更新和分化能力使人们能够研究细胞分化过程、筛选小分子药物、模拟人类疾病,并测试再生医学。为了整合基因编辑和干细胞技术,迫切需要以可编程的 DNA 靶向酶和/或外源性核酸模板的形式实现必要分子工具的高效传递。此外,递药载体本身对基因编辑程序的性能和精度的影响是另一个需要考虑的关键参数。由重组缺陷型病毒组成的病毒载体正在被深入研究,以期在体外和体内实验方案中实现有效的基因编辑工具传递和人类细胞的精确基因编辑。在这篇综述中,我们专注于腺病毒载体在靶向遗传操纵人类干细胞、祖细胞及其分化后代方面所扮演的日益重要的角色。作为序幕,我们提供了主要基因编辑原理和腺病毒载体平台的概述,并以讨论利用腺病毒载体、基因编辑和干细胞技术所带来的可能性结束。