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Published Online:https://doi.org/10.2217/14622416.6.5.527

Cell-based microarrays were first described by Ziauddin and Sabatini in 2001 as a novel method for performing high-throughput screens of gene function. In this study, expression vectors containing the open reading frame of human genes were printed onto glass microscope slides to form a microarray. Transfection reagents were added pre- or post-spotting, and cells grown over the surface of the array. They demonstrated that cells growing in the immediate vicinity of the expression vectors underwent ‘reverse transfection’, and that subsequent alterations in cell function could then be detected by secondary assays performed on the array. Subsequent publications have adapted the technique to a variety of applications, and have also shown that the approach works when arrays are fabricated using short interfering RNAs and compounds. The potential of this method for performing analyses of gene function and for identifying novel therapeutic agents has been clearly demonstrated, and current efforts are focused on improving and harnessing this technology for high-throughput screening applications.

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

Bibliography

  • Wodicka L, Dong H, Mittmann M, Ho MH, Lockhart DJ: Genome-wide expression monitoring in Saccharomyces cerevisiae.Nature Biotechnol.15, 1359–1367 (1997).
  • DeRisi JL, Iyer VR, Brown PO: Exploring the metabolic and genetic control of gene expression on a genomic scale. Science278, 680–686 (1997).
  • Pollack JR, Perou CM, Alizadeh AA et al.: Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nature Genet.23, 41–46 (1999).
  • Pinkel D, Segraves R, Sudar D et al.: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genet.20, 207–211 (1998).
  • Mei R, Galipeau PD, Prass C et al.: Genome-wide detection of allelic imbalance using human SNPs and high density DNA arrays. Genome Res.10, 1126–1137 (2000).
  • Hacia JG, Fan JB, Ryder O et al.: Determination of ancestral alleles for human single-nucleotide polymorphisms using high-density oligonucleotide arrays. Nature Genet.22, 164–167 (1999).
  • Shi MH, Maier S, Nimmrich I et al.: Oligonucleotide-based microarray for DNA methylation analysis: Principles and applications. J. Cell. Biochem. 88 (2003).
  • Ren B, Robert F, Wyrick JJ et al.: Genome-wide location and function of DNA binding proteins. Science290, 2306–2309 (2000).
  • Pavlickova P, Schneider EM, Hug H: Advances in recombinant antibody microarrays. Clin. Chim. Acta.343, 17–35 (2004).
  • 10  Uetz P: Two-hybrid arrays. Curr. Opin. Chem. Biol. 6(1), 57–62 (2001).
  • 11  Fukui S, Feizi R, Galustian C, Lawson AM, Wengang C: Oligosaccharide microarrays for high-throughput detection and specificity assignments of carbohydrate-protein interactions. Nature Biotechnol.20, 1011–1017 (2002).
  • 12  MacBeath G, Koehler AN, Schreiber SL: Printing small molecules as microarrays and detecting protein-ligand interactions en masse.J. Am. Chem. Soc.121, 7967–7968 (1999).
  • 13  Ziauddin J, Sabatini DM: Microarrays of cells expressing defined cDNAs. Nature411, 107–110 (2001).•• First cell-based microarray paper.
  • 14  Webb BL, Diaz B, Martin GS, Lai F: A reporter system for reverse transfection cell arrays. J. Biomol. Screen.8, 620–623 (2003).
  • 15  Mishina YM, Wilson CJ, Bruett L et al.: Multiplex GPCR assay in reverse transfection cell microarrays. J. Biomol. Screen.9, 196–207 (2004).
  • 16  Delehanty JB, Shaffer KM, Lin B: Transfected cell microarrays for the expression of membrane-displayed single-chain antibodies. Anal. Chem.76, 7323–7328 (2004).• First paper describing antibody screening using cell-based microarrays.
  • 17  Palmer E, Freeman T: Investigation into the use of C- and N-terminal GFP fusion proteins for subcellular localization studies using reverse transfection microarrays. Comp. Funct. Genomics5, 324–353 (2004).
  • 18  Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature391, 806–811 (1998).•• First RNAi paper.
  • 19  Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T: Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J.20, 6877–6888 (2001).
  • 20  Hammond SM, Bernstein E, Beach D, Hannon GJ: An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature404, 293–296 (2000).
  • 21  Stevenson M: Therapeutic potential of RNA interference. N. Engl. J. Med.351, 1772–1777 (2004).
  • 22  Huppi K, Martin SE, Caplen NJ: Defining and assaying RNAi in mammalian cells. Mol. Cell17, 1–10 (2005).
  • 23  Gil J, Esteban M: Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): mechanism of action. Apoptosis5, 107–114 (2000).
  • 24  Elbashir SM, Lendeckel W, Tuschl T: RNA interference is mediated by 21-and 22-nucleotide RNAs. Genes Dev.15, 188–200 (2000).
  • 25  Brummelkamp TR, Bernards R, Agami R: A system for stable expression of short interfering RNAs in mammalian cells. Science296, 550–553 (2002).
  • 26  Baghdoyan S, Roupoiz Y, Pitaval A et al.: Quantitative analysis of highly parallel transfection in cell microarrays. Nucleic Acids Res.32, e77 (2004).
  • 27  Mousses S, Caplen NJ, Cornelison R et al.: RNAi microarray analysis in cultured mammalian cells. Genome Res.13, 2341–2347 (2003).• First RNAi cell-based microarray paper, published back to back with Kumar and colleagues (2003).
  • 28  Silva JM, Mizuno H, Brady A, Lucito R, Hannon GJ: RNA interference microarrays: High-throughput loss-of-function genetics in mammalian cells. Proc. Natl Acad. Sci. USA101, 6548–6552 (2004).
  • 29  Erfle H, Simpson JC, Bastiaens PIH, Pepperkok R: siRNA cell arrays for high-content screening microscopy. BioTechniques37, 454–462 (2004).
  • 30  Kumar R, Conklin DS, Mittal V: High-throughput selection of effective RNAi probes for gene silencing. Genome Res.13, 2333–2340 (2003).• First RNAi cell-based microarray paper, published back to back with Mousses and co-workers (2003).
  • 31  Wheeler DB, Bailey SN, Guertin DA, Carpenter AE, Higgins CO, Sabatini DM: RNAi living-cell microarrays for loss-of-function screens in Drosophila melanogaster cells. Nature Methods1, 1–6 (2004).
  • 32  Bailey SN, Sabatini DM, Stockwell BR: Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens. Proc. Natl Acad. Sci. USA101, 16144–16149 (2004).• First paper describing compound drug screens using cell-based microarrays.
  • 33  Chang F, Lee C, Chen M et al.: Surfection: a new platform for transfected cell arrays. Nucleic Acids Res.32, e33 (2004).
  • 34  Redmond TM, Ren X, Kubish G, Atkins S, Low S, Uhler MD: Microarray transfection analysis of transcriptional regulation by cAMP-dependent protein kinase. Mol. Cell Proteomics3(8), 770–779 (2004).
  • 35  Kato K, Umezawa K, Funeriu DP, Miyake M, Miyake J, Nagamune T: Immobilized culture of nonadherent cells on an oleyl poly(ethylene glycol) ether-modified surface. BioTechniques35, 1014–1021 (2003).
  • 36  Kato K, Umezawa K, Miyake M, Miyake J, Nagamune T: Transfection microarray of nonadherent cells on an aleyl poly (ethylene glycol) ether-modified glass slide. BioTechniques37, 444–452 (2004).
  • 37  Delehanty JB, Shaffer KM, Lin B: A comparison of microscope slide substrates for use in transfected cell microarrays. Biosens. Bioelectron.20, 773–779 (2004).
  • 38  Yamauchi F, Kato K, Iwata H: Micropatterned, self-assembled monolayers for fabrication of transfected cell microarrays. Biochim. Biophys. Acta1672, 138–147 (2004).
  • 39  How SE, Yingyongnarongkul B, Fara MA, Diaz-Mochon JJ, Mittoo S, Bradley M: Polyplexes and lipoplexes for mammalian gene delivery: from traditional to microarray screening. Comb. Chem. High Throughput Screen.8, 423–430 (2004).
  • 40  Isalan M, Santori MI, Gonzalez C, Serrano L: Localized transfection on arrays of magnetic beads coated with PCR products. Nature Methods2, 113–118 (2005).
  • 41  Yamauchi S, Kato K, Iwata H: Spatially and temporally controlled gene transfer by electroporation into adherent cells on plasmid DNA-loaded electrodes. Nucleic Acids Res.32, e187 (2004).
  • 42  Yoshikawaa T, Uchimuraa E, Kishia M, Funeriua DP, Miyakea M, Miyakeb J: Transfection microarray of human mesenchymal stem cells and on-chip siRNA gene knockdown. J. Control. Release96, 227–232 (2004).
  • 43  Zemanova L, Schenk A, Valler MJ, Nienhaus U, Heilker R: Confocal optics microscope for biochemical and cellular high-throughput screening. Drug Discov. Today8, 1085–1093 (2003).
  • 44  Starkuviene V, Liebel U, Simpson JC et al.: High-content screening microscopy identifies novel proteins with a putative role in secretory membrane traffic. Genome Res.14, 1948–1956 (2004).
  • 45  Liebel U, Starkuviene V, Erfle H et al.: A microscope-based screening platform for large-scale functional protein analysis in intact cells. FEBS Lett.554, 394–398 (2003).
  • 46  Bailey SN, Wu RZ, Sabatini DM: Applications of transfected cell microarrays in high-throughput drug discovery. Drug Discov. Today7(Suppl.), S113–S118 (2002).
  • 47  Carpenter AE, Sabatini DM: Systematic genome-wide screens of gene function. Nature Rev. Genet.5, 11–22 (2004).
  • 48  Lehner B, Fraser AG: Microarrays have revolutionized gene expression studies and are set to do the same for genome-wide RNA interference screens. Nature Methods1, 103–104 (2004).
  • 49  Vanhecke D, Janitz M: High-throughput gene silencing using cell arrays. Oncogene23, 8353–8358 (2004).
  • 50  Wu RZ, Bailey SN, Sabatini DM: Cell-biological applications of transfected-cell microarrays. Trends Cell Biol.12, 485–488 (2002).
  • 51  Wheeler DB, Carpenter AE, Sabatini DM: Cell microarrays and RNA interference chip away at gene function. Nature Genet.37, S25–S30 (2005).
  • 52  Krenkova J, Foret F: Immobilized microfluidic enzymatic reactors. Electrophoresis25, 3550–5363 (2004).
  • 53  Park TH, Shuler ML: Integration of cell culture and microfabrication technology. Biotechnol. Prog.19, 243–253 (2003).
  • 54  Reboul J, Vaglio P, Rual J et al.: C. elegans ORFeome version 1.1 experimental verification of the genome annotation and resource for proteome-scale protein expression. Nature Genet.34, 35–41 (2003).
  • 55  Stapleton M, Carlson J, Brokstein P et al.: A Drosophila full-length cDNA resource. Genome Biol.2, research 0080.0–0080.8 (2002).
  • 56  Brizuela L, Richardson A, Marsischky G, Labaer J: The FLEXGene repository: Exploiting the fruits of the genome projects by creating a needed resource to face the challenges of the post-genomic era. Arch. Med. Res.33, 318–324 (2002).
  • 57  Gerhard DS, Wagner L, Feingold EA et al.: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res.14, 2121–2127 (2004).
  • 58  Mewes HW, Amid C, Arnold R et al.: MIPS: analysis and annotation of proteins from whole genomes. Nucleic Acids Res.32, D41–44 (2004).
  • 59  Strausberg RL, Feingold EA, Grouse LH et al.: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. PNAS99, 16899–16903 (2002).
  • 60  Kamath RS, Fraser AG, Dong Y et al.: Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature421, 231–237 (2003).
  • 61  Berns K, Hijmans EM, Mullenders J et al.: A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature428, 431–437 (2004).
  • 62  Paddison PJ, Silva JM, Conklin DS et al.: A resource for large-scale RNA-interference-based screens in mammals. Nature428, 427–431 (2004).

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