Genetically Modified Mouse Models in ADME Studies

Jiang, Xi Ling; Yu, Aiming

doi:10.1002/9781118180778.ch28

Cited by 1 publication

(2 citation statements)

References 165 publications

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“…In Vivo. Prior to the CRISPR-Cas9 technology, in vivo knockout P450 models, humanized P450 models (where animals express the human P450 ortholog), or chimeric models (where human hepatocytes were transplanted and allowed to repopulate the host liver) were used to study ADME-and toxicity-related problems (Tateno et al, 2004;Cheung and Gonzalez, 2008;Hasegawa et al, 2011;Jiang and Yu, 2012;Kazuki et al, 2013;Scheer et al, 2013). However, the major applications of these models involve, e.g., studies of developmental or physiologic functions, disease mechanisms, validation of target genes, identification of off-targeted effects for drugs and drug candidates, etc.…”

Section: Drug-metabolizing Enzymesmentioning

confidence: 99%

“…These models allowed studies of the role of a specific transporter in the presence of all other mechanisms influencing drug disposition in vivo, such as drug uptake, distribution, metabolism, and efflux. For overviews of in vivo knockout transporter models, see Jiang and Yu (2012) and Tang et al (2013). Prominent examples of the applicability of single and multiple Fig.…”

Section: Drug Transportersmentioning

confidence: 99%

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

et al. 2018

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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.

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