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High-throughput and combinatorial gene expression on a chip for metabolism-induced toxicology screening.

ABSTRACT: Differential expression of various drug-metabolizing enzymes (DMEs) in the human liver may cause deviations of pharmacokinetic profiles, resulting in interindividual variability of drug toxicity and/or efficacy. Here, we present the 'Transfected Enzyme and Metabolism Chip' (TeamChip), which predicts potential metabolism-induced drug or drug-candidate toxicity. The TeamChip is prepared by delivering genes into miniaturized three-dimensional cellular microarrays on a micropillar chip using recombinant adenoviruses in a complementary microwell chip. The device enables users to manipulate the expression of individual and multiple human metabolizing-enzyme genes (such as CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2E1 and UGT1A4) in THLE-2 cell microarrays. To identify specific enzymes involved in drug detoxification, we created 84 combinations of metabolic-gene expressions in a combinatorial fashion on a single microarray. Thus, the TeamChip platform can provide critical information necessary for evaluating metabolism-induced toxicity in a high-throughput manner.

SUBMITTER: Kwon SJ

PROVIDER: S-EPMC4132844 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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High-throughput and combinatorial gene expression on a chip for metabolism-induced toxicology screening.

Kwon Seok Joon SJ Lee Dong Woo DW Shah Dhiral A DA Ku Bosung B Jeon Sang Youl SY Solanki Kusum K Ryan Jessica D JD Clark Douglas S DS Dordick Jonathan S JS Lee Moo-Yeal MY

Nature communications 20140506

Differential expression of various drug-metabolizing enzymes (DMEs) in the human liver may cause deviations of pharmacokinetic profiles, resulting in interindividual variability of drug toxicity and/or efficacy. Here, we present the 'Transfected Enzyme and Metabolism Chip' (TeamChip), which predicts potential metabolism-induced drug or drug-candidate toxicity. The TeamChip is prepared by delivering genes into miniaturized three-dimensional cellular microarrays on a micropillar chip using recombi ...[more]

PMID: 24799042

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Dataset Information

High-throughput and combinatorial gene expression on a chip for metabolism-induced toxicology screening.

Publications

High-throughput and combinatorial gene expression on a chip for metabolism-induced toxicology screening.

Similar Datasets

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