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CRISPR-Cas9: A New Addition to the Drug Metabolism and Disposition Tool Box
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala Univ, Dept Pharm, Box 580, SE-75123 Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Univ Med Greifswald, Ctr Drug Absorpt & Transport, Dept Clin Pharmacol, Greifswald, Germany.
Univ Med Greifswald, Ctr Drug Absorpt & Transport, Dept Clin Pharmacol, Greifswald, Germany.
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2018 (English)In: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 46, no 11, p. 1776-1786Article, review/survey (Refereed) Published
Abstract [en]

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 ADME and ADME-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 ADME 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.

Place, publisher, year, edition, pages
The American Society for Pharmacology and Experimental Therapeutics , 2018. Vol. 46, no 11, p. 1776-1786
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-386345DOI: 10.1124/dmd.118.082842ISI: 000452484200034PubMedID: 30126863OAI: oai:DiVA.org:uu-386345DiVA, id: diva2:1361542
Funder
Swedish Research Council, 1951Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-16Bibliographically approved

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Karlgren, MariaSimoff, IvailoArtursson, Per

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