title: 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.
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Kwon
authors.affiliation: Samsung Electro-Mechanics Co, Central R & D Institute, Suwon 443-743, South Korea.
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Lee
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Dhiral A
authors.initials: DA
authors.lastname: Shah
authors.affiliation: Samsung Electro-Mechanics Co, Central R & D Institute, Suwon 443-743, South Korea.
authors.forename: Bosung
authors.initials: B
authors.lastname: Ku
authors.affiliation: Samsung Electro-Mechanics Co, Central R & D Institute, Suwon 443-743, South Korea.
authors.forename: Sang Youl
authors.initials: SY
authors.lastname: Jeon
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Kusum
authors.initials: K
authors.lastname: Solanki
authors.affiliation: Solidus Biosciences Inc., 409 Illinois Street, Suite 2073, San Francisco, California 94158, USA.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Ryan
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California at Berkeley, Berkeley, California 94720, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Clark
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.affiliation: 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.
authors.forename: Moo-Yeal
authors.initials: MY
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015870:Gene Expression; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism
chemical_list: D003577:Cytochrome P-450 Enzyme System