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Research ArticleSpecial Section – New Models in Drug Metabolism and Transport
Open Access

CRISPR-Cas9: A New Addition to the Drug Metabolism and Disposition Tool Box

M. Karlgren, I. Simoff, M. Keiser, S. Oswald and P. Artursson
Drug Metabolism and Disposition November 2018, 46 (11) 1776-1786; DOI: https://doi.org/10.1124/dmd.118.082842
M. Karlgren
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.)
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I. Simoff
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.)
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M. Keiser
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.)
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S. Oswald
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.)
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P. Artursson
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.)
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Abstract

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.

Footnotes

    • Received June 1, 2018.
    • Accepted August 3, 2018.
  • This work is supported by The Swedish Fund for Research without Animal Experiment (Approval Number 0004) to M.Ka.; the Magnus Bergvall Foundation (Approval No. 2305) to M.Ka.; and the Swedish Research Council (Approval No. 1951) to P.A.

  • https://doi.org/10.1124/dmd.118.082842.

  • Copyright © 2018 by The Author(s)

This is an open access article distributed under the CC BY-NC Attribution 4.0 International license.

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Drug Metabolism and Disposition: 46 (11)
Drug Metabolism and Disposition
Vol. 46, Issue 11
1 Nov 2018
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Research ArticleSpecial Section – New Models in Drug Metabolism and Transport

CRISPR-Cas9 in Drug Metabolism and Disposition

M. Karlgren, I. Simoff, M. Keiser, S. Oswald and P. Artursson
Drug Metabolism and Disposition November 1, 2018, 46 (11) 1776-1786; DOI: https://doi.org/10.1124/dmd.118.082842

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Research ArticleSpecial Section – New Models in Drug Metabolism and Transport

CRISPR-Cas9 in Drug Metabolism and Disposition

M. Karlgren, I. Simoff, M. Keiser, S. Oswald and P. Artursson
Drug Metabolism and Disposition November 1, 2018, 46 (11) 1776-1786; DOI: https://doi.org/10.1124/dmd.118.082842
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    • How Does CRISPR-Cas9 Work?
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