Department of Pharmacy (M.Ka., P.A.), Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Department of Pharmacy (I.S.), and Science for Life Laboratory (P.A.), Uppsala University, Uppsala, Sweden; and Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Germany (M.Ke., S.O.)
Department of Pharmacy (M.Ka., P.A.), Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Department of Pharmacy (I.S.), and Science for Life Laboratory (P.A.), Uppsala University, Uppsala, Sweden; and Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Germany (M.Ke., S.O.).
Drug Metab Dispos. 2018 Nov;46(11):1776-1786. doi: 10.1124/dmd.118.082842. Epub 2018 Aug 20.
Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9), i.e., CRISPR-Cas9, has been extensively used as a gene-editing technology during recent years. Unlike earlier technologies for gene editing or gene knockdown, such as zinc finger nucleases and RNA interference, CRISPR-Cas9 is comparably easy to use, affordable, and versatile. Recently, CRISPR-Cas9 has been applied in studies of drug absorption, distribution, metabolism, and excretion (ADME) and for ADME model generation. To date, about 50 papers have been published describing in vitro or in vivo CRISPR-Cas9 gene editing of and -related genes. Twenty of these papers describe gene editing of clinically relevant genes, such as ATP-binding cassette drug transporters and cytochrome P450 drug-metabolizing enzymes. With CRISPR-Cas9, the ADME tool box has been substantially expanded. This new technology allows us to develop better and more predictive in vitro and in vivo ADME models and map previously underexplored genes and gene families. In this mini-review, we give an overview of the CRISPR-Cas9 technology and summarize recent applications of CRISPR-Cas9 within the ADME field. We also speculate about future applications of CRISPR-Cas9 in ADME research.
近年来，成簇规律间隔短回文重复序列（CRISPR）-CRISPR 相关蛋白 9（Cas9），即 CRISPR-Cas9，已被广泛用作基因编辑技术。与早期的基因编辑或基因敲低技术（如锌指核酸酶和 RNA 干扰）相比，CRISPR-Cas9 更易于使用、经济实惠且功能多样。最近，CRISPR-Cas9 已应用于药物吸收、分布、代谢和排泄（ADME）研究和 ADME 模型生成。迄今为止，已有约 50 篇论文描述了体外或体内 CRISPR-Cas9 对和相关基因的基因编辑。其中 20 篇论文描述了对临床相关基因（如 ATP 结合盒药物转运体和细胞色素 P450 药物代谢酶）的基因编辑。有了 CRISPR-Cas9，ADME 工具包得到了极大扩展。这项新技术使我们能够开发更好、更具预测性的体外和体内 ADME 模型，并对以前研究较少的基因和基因家族进行基因编辑。在这篇小型综述中，我们概述了 CRISPR-Cas9 技术，并总结了 CRISPR-Cas9 在 ADME 领域的最新应用。我们还推测了 CRISPR-Cas9 在 ADME 研究中的未来应用。
