Lu Jian, Liu Jie, Guo Yuanqing, Zhang Yuanjin, Xu Yeye, Wang Xin
Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai 200051, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Acta Pharm Sin B. 2021 Oct;11(10):2973-2982. doi: 10.1016/j.apsb.2021.01.007. Epub 2021 Jan 7.
The 2020 Nobel Prize in Chemistry recognized CRISPR-Cas9, a super-selective and precise gene editing tool. CRISPR-Cas9 has an obvious advantage in editing multiple genes in the same cell, and presents great potential in disease treatment and animal model construction. In recent years, CRISPR-Cas9 has been used to establish a series of rat models of drug metabolism and pharmacokinetics (DMPK), such as , , gene knockout rats. These new rat models are not only widely used in the study of drug metabolism, chemical toxicity, and carcinogenicity, but also promote the study of DMPK related mechanism, and further strengthen the relationship between drug metabolism and pharmacology/toxicology. This review systematically introduces the advantages and disadvantages of CRISPR-Cas9, summarizes the methods of establishing DMPK rat models, discusses the main challenges in this field, and proposes strategies to overcome these problems.
2020年诺贝尔化学奖表彰了CRISPR-Cas9，这是一种超具选择性且精确的基因编辑工具。CRISPR-Cas9在编辑同一细胞中的多个基因方面具有明显优势，在疾病治疗和动物模型构建中展现出巨大潜力。近年来，CRISPR-Cas9已被用于建立一系列药物代谢和药代动力学（DMPK）大鼠模型，如 、 、 基因敲除大鼠。这些新型大鼠模型不仅广泛应用于药物代谢、化学毒性和致癌性研究，还推动了DMPK相关机制的研究，并进一步加强了药物代谢与药理学/毒理学之间的联系。本综述系统介绍了CRISPR-Cas9的优缺点，总结了建立DMPK大鼠模型的方法，讨论了该领域的主要挑战，并提出了克服这些问题的策略。
