Centre for Drug and Herbal Development, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
CRISPR J. 2023 Jun;6(3):196-215. doi: 10.1089/crispr.2023.0013. Epub 2023 May 19.
Stem cells such as induced pluripotent stem cells, embryonic stem cells, and hematopoietic stem and progenitor cells are growing in importance in disease modeling and regenerative medicine. The applications of CRISPR-based gene editing to create a mélange of disease and nondisease stem cell lines have further enhanced the utility of this innately versatile group of cells in the studies of human genetic disorders. Precise base edits can be achieved using a variety of CRISPR-centric approaches, particularly homology-directed repair and the recently developed base editors and prime editors. Despite its much-touted potential, editing single DNA bases is technically challenging. In this review, we discuss the strategies for achieving exact base edits in the creation of various stem cell-based models for use in elucidating disease mechanisms and assessing drug efficacy, and the unique characteristics of stem cells that warrant special considerations.
在疾病建模和再生医学中，诱导多能干细胞、胚胎干细胞和造血干细胞和祖细胞等干细胞的重要性日益增加。基于 CRISPR 的基因编辑技术的应用可以创建各种疾病和非疾病干细胞系的混合物，进一步增强了这群固有多功能细胞在人类遗传疾病研究中的应用。使用各种以 CRISPR 为中心的方法，特别是同源定向修复和最近开发的碱基编辑器和 Prime 编辑器，可以实现精确的碱基编辑。尽管有很大的潜力，但编辑单个 DNA 碱基在技术上具有挑战性。在这篇综述中，我们讨论了在创建各种基于干细胞的模型以阐明疾病机制和评估药物疗效时实现精确碱基编辑的策略，以及干细胞的独特特征需要特别考虑。
