• About Dharmacon

    We are part of Thermo Fisher Scientific, the world leader in serving science. Dharmacon Research, Inc. was founded in 1995 to develop and commercialize a new technology for RNA oligonucleotide synthesis. In March of 2004, Dharmacon became a wholly owned subsidiary of Fisher Scientific International, Inc. In November of 2006, Fisher Scientific International, Inc. merged with Thermo Electron Corporation to become Thermo Fisher Scientific.

    History

    At the time of its founding, Dharmacon primarily served research areas with applications requiring high-quality synthetic RNA oligonucleotides. The 2'-ACE chemistry lends itself to high yields and oligo lengths that were difficult, if not impossible, to obtain with other synthesis chemistries.

    When RNA interference (RNAi) emerged in the late 1990's, Dharmacon was poised to provide RNAi-related products to the multitude of academic and industry researchers. Dharmacon became an important resource for those investigating the mechanisms of siRNA (small interfering RNA)-induced gene knockdown, and rapidly became a recognized leader in siRNA design for potency and specificity. In 2005 Dharmacon founded the RNAi Global Initiative (www.rnaiglobal.org) to advance RNAi screening as a functional genomics tool. With its membership now exceeding 50 leading academic and government research institutions, RNAi Global continues to lead collaborative efforts to drive best-practice and excellence in RNAi -driven discovery.

    Key Technologies & Achievements

    Dharmacon's expertise in bioinformatics, RNA biology, and synthesis chemistry allowed it to develop a complete line of products for the RNAi researcher, including the first rationally designed siRNA, the siGENOME siRNA collection, targeting all unique genes in the human, mouse, and rat genomes. Further breakthroughs came in chemical modifications for siRNA specificity, and novel molecules for microRNA modulation.

    Key Publications

    S.A. Scaringe, F.E. Wincott, M.H. Caruthers
    Novel RNA Synthesis Method Using 5'-O-Silyl-2'-O'-orthoester Protecting Groups
    J. Am. Chem. Soc. 120, 11820 (1998).

    M. Meroueh, P.J. Grohar, J. Qiu, J. SantaLucia Jr, S.A. Scaringe, C.S. Chow
    Unique structural and stabilizing roles for the individual pseudouridine residues in the 1920 region of Escherichia coli 23S rRNA
    Nucleic Acids Res. 2000 May 15;28(10):2075-83.

    S. A. Scaringe
    RNA oligonucleotide synthesis via 5'-silyl-2'-orthoester chemistry.
    Methods. 2001 Mar;23(3):206-17.

    Q. F. Boese , S. A. Scaringe and W. S. Marshall
    siRNA as a tool for streamlining functional genomic studies
    Targets. June 2003; 2(3): 93-100.

    J. Harborth, S.M. Elbashir, K. Vandenburgh, H. Manninga, S.A. Scaringe, K Weber, and T. Tuschl
    Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing.
    Antisense Nucleic Acid Drug Development. 2003 Apr;13(2):83-105.

    Z.Y. Jiang, Q.L. Zhou, K.A. Coleman, M. Chouinard, Q. Boese, M.P. Czech
    Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing
    PNAS. 2003 Jun 24;100(13):7569-74.

    A. Khvorova, A. Reynolds, S.D. Jayasena
    Functional siRNAs and miRNAs Exhibit Strand Bias
    Cell (115): 209–216.

    L. Benimetskaya, J. C. Lai, A. Khvorova, S. Wu, E. Hua, P. Miller, L. Zhang and C. A. Stein
    Relative Bcl-2 Independence of Drug-Induced Cytotoxicity and Resistance in 518A2 Melanoma Cells
    Clinical Cancer Research. 2004 Dec 15;10(24):8371-9.

    Q. Boese, W. Marshall, S. Scaringe
    Strategies for synthesizing small interfering RNA (siRNA)
    RNA Interference (RNAi)~Nuts & Bolts of siRNA Technology

    F. Huang, A. Khvorova, W. Marshall, A. Sorkin
    Analysis of clathrin-mediated endocytosis of EGF receptor by RNA interference
    J Biol Chem. 2004 Apr 16;279(16):16657-61.

    A.C. Hsieh, R. Bo, J. Manola, F. Vazquez, O. Bare, A. Khvorova, S. Scaringe, W.S. Sellers
    A library of siRNA duplexes targeting the phosphoinositide 3-kinase pathway: determinants of gene silencing for use in cell-based screens
    Nucleic Acids Research. 2004 Feb 9;32(3):893-901.

    T. Li, C.Y. Chang, D.Y. Jin, P.J. Lin, A. Khvorova, D.W. Stafford
    Identification of the gene for vitamin K epoxide reductase.
    Nature. 2004 Feb 5;427(6974):541-4.

    W.S. Marshall, R.J. Kaiser
    Recent advances in the high-speed solid phase synthesis of RNA
    Curr Opin Chem Biol. 2004 Jun;8(3):222-9.

    J.T. Miller, A. Khvorova, S.A. Scaringe, S.F. Le Grice
    Synthetic tRNALys,3 as the replication primer for the HIV-1HXB2 and HIV-1Mal genomes
    Nucleic Acids Res. 2004 Sep 1;32(15):4687-95.

    A. Reynolds, D. Leake, Q. Boese, S. Scaringe, W.S. Marshall, A. Khvorova
    Rational siRNA design for RNA interference.
    Nat Biotechnol. 2004 Mar;22(3):326-30.

    J. Spellberg, M. Deines, W. Marshall, Q. Boese
    Gene silencing taken further
    Global Discovery and Development. 2004: 31.

    S. A. Scaringe, D. Kitchen, R. Kaiser, W. Marshall
    Preparation of 5'-Silyl-2'-Orthoester Ribonucleosides for Use in Oligoribonucleotide Synthesis
    Current Protocols in Nucleic Acid Chemistry. 1(2):2.10(1-5)

    J.S. Weinger, D. Kitchen, S.A. Scaringe, S.A. Strobel, G.W. Muth
    Solid phase synthesis and binding affinity of peptidyl transferase transition state mimics containing 2'-OH at P-site position A76
    Nucleic Acids Res. 2004 Mar 3;32(4):1502-11.

    J. Karpilow, D. Leake and B. Marshall
    siRNA: Enhanced Functionality Through Rational Design and Chemical Modificaiton
    Pharmagenomics. March/April 2004. 32-40.

    Q. Boese. W. Marshall, A. Khvorova
    Design and Synthesis of Small Interfering RNA (siRNA)
    RNA Interference: From Basic Science to Drug Development

    Q. Boese, A. Reynolds, W. S. Marshall
    Basics of siRNA design and chemical synthesis
    Gene Silencing by RNA Interference

    A. Raffo, J.C. Lai, C.A. Stein, P. Miller, S.A. Scaringe, A. Khvorova, L. Benimetskaya
    Antisense RNA down-regulation of bcl-2 expression in DU145 prostate cancer cells does not diminish the cytostatic effects of G3139 (Oblimersen)
    Clin Cancer Res. 2004 May 1;10(9):3195-206.

    Q. Boese, D. Leake, A. Reynolds, S. Read, S. Scaringe, W. Marshall, A. Khvorova
    Mechanistic insights aid computational siRNA design
    Methods in Enzymology

    A. Vermeulen, L. Behlen, A. Reynolds, A. Wolfson, W. S. Marshall, J. Karpilow, A. Khvorova
    The Contributions of dsRNA Structure to Dicer Specificity and Efficiency
    RNA Journal, 2005 May;11(5):674-82.

    Y. Fedorov, A. King, E. Anderson, J. Karpilow, D. Ilsley, W. Marshall, A. Khvorova
    Different delivery methods-different expression profiles
    Nature Methods. 2005 Apr;2(4):241

    A. Khvorova, Q. Boese, and W. S. Marshall
    Rational siRNA Design for RNA Interference: Optimizations for Therapeutic Use and Current Applications
    Modern Biopharmaceuticals

    J.C. Lai, L. Benimetskaya, A. Khvorova, S. Wu, E. Hua, P. Miller, C.A. Stein
    Phosphorothioate oligodeoxynucleotides and G3139 induce apoptosis in 518A2 melanoma cells
    Mol Cancer Ther. 2005 Feb;4(2):305-15.

    S.A. Hartsel, D.E. Kitchen, S.A. Scaringe. W.S. Marshall
    RNA oligonucleotide synthesis via 5'-silyl-2'-orthoester chemistry.
    Methods Mol Biol. 2005;288:33-50.

    A. Reynolds, E. M. Anderson, A. Vermeulen, Y. Fedorov, K. Robinson, D. Leake, J. Karpilow, W. S. Marshall, and A. Khvorova
    Induction of the interferon response by siRNA is cell type and duplex length dependent
    RNA, 2006 12(6):988-993.

    Y. Fedorov, E. M. Anderson, A. Birmingham, A. Reynolds, J. Karpilow, K. Robinson, D. Leake, W. S. Marshall, A. Khvorova
    Off-Targeting By siRNA Can Induce Toxic Phenotype

    A. L. Jackson, J. Burchard, D. Leake, A. Reynolds, J. Schelter, J. Guo, J. M. Johnson, L. Lim, J. Karpilow, K. Nichols, W. S. Marshall, A. Khvorova, and P. S. Linsley
    Position-specific Chemical Modification Increases Specificity of siRNA-mediated Gene Silencing
    RNA, 2006 12(7):1197-1205.

    E.M. Anderson, P. Miller, D. Ilsley, W. Marshall, A. Khvorova, C.A. Stein, L. Benimetskaya
    Gene profiling study of G3139- and Bcl-2-targeting siRNAs identifies a unique G3139 molecular signature.
    Cancer Gene Therapy, 2006 13(4):406-14.

    K. Brown and D. Samarsky
    RNAi off-targeting: Light at the end of the tunnel
    Journal of RNAi and Gene Silencing, 2006 2(2): 175-177.

    A. Birmingham, E.M. Anderson, A. Reynolds, D. Ilsley-Tyree, D. Leake, Y. Fedorov, S. Baskerville, E. Maksimova, K. Robinson, J. Karpilow, W.S. Marshall, A. Khvorova
    3'-UTR seed matches, but not overall identity, are associated with RNAi off -targets
    Nature Methods, 2006 3: 199 - 204.

    A. Vermeulen, B. Robertson, A. B. Dalby, W. S. Marshall, Jon Karpilow, D. Leake, A. Khvorova, and S. Baskerville
    Double-stranded regions are essential design components of potent inhibitors of RISC function
    RNA, May 2007. 13: 723 - 730.

    A. Birmingham, E. Anderson, K. Sullivan, A. Reynolds, Q. Boese, D. Leake, J. Karpilow, and A. Khvorova
    A protocol for designing siRNAs with high functionality and specificity
    Nature Protocols, 2007 2(9):2068-2078.

    E. M. Anderson, A. Birmingham, S. Baskerville, A. Reynolds, E. Maksimova, D. Leake, Y. Fedorov, J. Karpilow, and A. Khvorova
    Experimental validation of the importance of seed complement frequency to siRNA specificity
    RNA, May 2008. 14: 853-861.

    F.J. Smith, R.P. Hickerson, J.M. Sayers, R.E. Reeves, C.H. Contag, D. Leake, RL Kaspar, and W.H. McLean.
    Development of therapeutic siRNAs for pachyonychia congenita.
    J Invest Dermatol, Jan 2008. 128(1): 50-8.

    K.J. Simpson, L.M. Selfors, J.B., A. Reynolds, D. Leake, A. Khvorova, and J.S. Brugge.
    Identification of genes that regulate epithelial cell migration using an siRNA screening approach.
    Nat Cell Biol, Oct 2008. 10: 1027 - 1038.

    E. Anderson, Q. Boese, A. Khvorova, J. Karpilow
    Identifying siRNA-Induced Off-Targets by Microarray Analysis.
    Methods in Molecular Biology, April 2008. 442:45-63.

    R.P. Hickerson, A.V. Vlassov, Q.W., D. Leake, H.I., E. Gonzalez-Gonzalez, C.H. Contag, B.H. Johnston, and R.L. Kaspar.
    Stability Study of Unmodified siRNA and Relevance to Clinical Use.
    Oligonucleotides, Oct 2008. Epub ahead of print.

    L. Baskin, S. Urschel, and B. Eiberger
    A novel ex-vivo application of RNAi for neuroscience.
    Biotechniques, Sep 2008. (3):338-9

    A. Schoolmeesters, T. Eklund, D. Leake, A. Vermeulen, Q. Smith, S. Force Aldred, Y. Fedorov
    Functional Profiling Reveals Critical Role for miRNA in Differentiation of Human Mesenchymal Stem Cells
    PLoS ONE, May 2009. 4(5): e5605.