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

Seok Joon Kwon, Dong Woo Lee, Dhiral A. Shah, Bosung Ku, Sang Youl Jeon, Kusum Solanki, Jessica D. Ryan, Douglas S. Clark, Jonathan S. Dordick, Moo Yeal Lee

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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.

Original languageEnglish
Article number3739
JournalNature Communications
Volume5
DOIs
StatePublished - 6 May 2014
Externally publishedYes

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