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Dharmacon Research, Inc. was founded in 1995 to develop and commercialize a new technology for RNA oligonucleotide synthesis. In 2006, Dharmacon became part of Thermo Fisher Scientific and in March of 2014, Dharmacon became part of GE Healthcare Life Sciences.
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.
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.
S.A. Scaringe, F.E. Wincott, M.H. CaruthersNovel 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
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.
Z. Zhang, J.E. Lee, et al.High-efficiency RNA cloning enables accurate quantification of miRNA expression by deep sequencing.
Genome Biology 14, R109 (2013).
Ž. Strezoska, A. Licon, et al.Optimized PCR Conditions and Increased shRNA Fold Representation Improve Reproducibility of Pooled shRNA Screens.
PloS One. 7, e42341 (2012).