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Nat Commun. 2014 May 6;5:3739. doi: 10.1038/ncomms4739.

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

Author information

1
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
2
Samsung Electro-Mechanics Co, Central R & D Institute, Suwon 443-743, South Korea.
3
Solidus Biosciences Inc., 409 Illinois Street, Suite 2073, San Francisco, California 94158, USA.
4
Department of Chemical and Biomolecular Engineering, University of California at Berkeley, Berkeley, California 94720, USA.
5
1] Solidus Biosciences Inc., 409 Illinois Street, Suite 2073, San Francisco, California 94158, USA [2] Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, Ohio 44115, USA.

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.

PMID:
24799042
PMCID:
PMC4132844
DOI:
10.1038/ncomms4739
[Indexed for MEDLINE]
Free PMC Article

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