Off-target analysis of control siRNA molecules reveals important differences in the cytokine profile and inflammation response of human fibroblasts

Oligonucleotides

Volumn 20, Issue 1, 2010, Pages 17-25

  Baum, Patrick ^a   Fundel Clemens, Katrin ^a   Kreuz, Sebastian ^a   Kontermann, Roland E ^b   Weith, Andreas ^a   Mennerich, Detlev ^a   Rippmann, Jörg F ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^b UNIVERSITY OF STUTTGART   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 24; INTERLEUKIN 8; INTERSTITIAL COLLAGENASE; SMALL INTERFERING RNA; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ANIMAL CELL CULTURE; ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; ENZYME RELEASE; FIBROBLAST; GENE EXPRESSION PROFILING; GENE TARGETING; GENETIC ANALYSIS; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; INFLAMMATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION;

ANIMALS; CELL LINE; CYTOKINES; ENZYME-LINKED IMMUNOSORBENT ASSAY; FIBROBLASTS; GENE EXPRESSION; HUMANS; INFLAMMATION; MATRIX METALLOPROTEINASE 1; MICE; NF-KAPPA B; RNA INTERFERENCE; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION;

EID: 77649100994     PISSN: 15454576     EISSN: None     Source Type: Journal    
DOI: 10.1089/oli.2009.0213     Document Type: Article

References (30)

1. AGGARWAL, S., TAKADA, Y., MHASHILKAR, A.M., SIEGER, K., CHADA, S., and AGGARWAL, B.B. (2004). Melanoma differentiation-associated gene-7/IL-24 gene enhances NF-kappa B activation and suppresses apoptosis induced by TNF. J. Immunol. 173, 4368-4376.
2. ANDERSON, E.M., BIRMINGHAM, A., BASKERVILLE, S., REYNOLDS, A., MAKSIMOVA, E., LEAKE, D., FEDOROV, Y., KARPILOW, J., and KHVOROVA, A. (2008). Experimental validation of the importance of seed complement frequency to siRNA specif city. RNA. 14, 853-861.
3. BENJAMINI, Y., DRAI, D., ELMER, G., KAFKAFI, N., and GOLANI, I. (2001). Controlling the false discovery rate in behaviour genetics research. Behav. Brain Res. 125, 279-284.
4. BIRMINGHAM, A., ANDERSON, E.M., REYNOLDS, A., ILSLEY-TYREE, D., LEAKE, D., FEDOROV, Y., BASKERVILLE, S., MAKSIMOVA, E., ROBINSON, K., KARPILOW, J., MARSHALL, W.S., and KHVOROVA, A. (2006). 3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods. 3, 199-204.
5. BORDEN, P., and HELLER, R.A. (1997). Transcriptional control of matrix metalloproteinases and the tissue inhibitors of matrix metalloproteinases. Crit. Rev. Eukaryot. Gene Expr. 7, 159-178.
6. CEKAITE, L., FURSET, G., HOVIG, E., and SIOUD, M. (2007). Gene expression analysis i n blood cells in response to u nmodif ed and 2′-modif ed siRNAs reveals TLR-dependent and independent effects. J. Mol. Biol. 365, 90-108.
7. CZAUDERNA, F., FECHTNER, M., DAMES, S., AYGUN, H., KLIPPEL, A., PRONK, G.J., GIESE, K., and KAUFMANN, J. (2003). Structural variations and stabilising modif cations of synthetic siRNAs in mammalian cells. Nucleic Acids Res. 31, 2705-2716.
8. DAHLGREN, C., ZHANG, H.Y., DU, Q., GRAHN, M., NORSTEDT, G., WAHLESTEDT, C., and LIANG, Z. (2008). Analysis of siRNA specif city on targets with double-nucleotide mismatches. Nucleic Acids Res. 36, e53.
9. DIEBOLD, S.S., MASSACRIER, C., AKIRA, S., PATUREL, C., MOREL, Y., and REIS E SOUSA, C. (2006). Nucleic acid agonists for Toll-like receptor 7 are def ned by the presence of uridine ribonucleotides. Eur. J. Immunol. 36, 3256-3267.
10. DOWLER, T., BERGERON, D., TEDESCHI, A.L., PAQUET, L., FERRARI, N., and DAMHA, M.J. (2006). Improvements in siRNA properties mediated by 2 ′-deoxy-2′-f uoro-beta-D-arabinonucleic acid (FANA). Nucleic Acids Res. 34, 1669-1675.
11. DU, P., KIBBE, W.A., and LIN, S.M. (2008). Lumi: a pipeline for processing Illumina microarray. Bioinformatics. 24, 1547-1548.
12. DU, Q., THONBERG, H., WANG, J., WAHLESTEDT, C., and LIANG, Z. (2005). A systematic analysis of the silencing effects of an active siRNA at all single-nucleotide mismatched target sites. Nucleic Acids Res. 33, 1671-1677.
13. HOCHBERG, Y., and BENJAMINI, Y. (1990). More powerful procedures for multiple signif cance testing. Stat. Med. 9, 811-818.
14. HORNUNG, V., GUENTHNER-BILLER, M., BOURQUIN, C., ABLASSER, A., SCHLEE, M., UEMATSU, S., NORONHA, A., MANOHARAN, M., AKIRA, S., DE FOUGEROLLES, A., ENDRES, S., and HARTMANN, G. (2005). Sequence-specif c potent induction of IFN-(alpha) by short interfering RNA in plas-macytoid dendritic cells through TLR7. Nat. Med. 11, 263-270.
15. JACKSON, A.L., BURCHARD, J., LEAKE, D., REYNOLDS, A., SCHELTER, J., GUO, J., JOHNSON, J.M., LIM, L., KARPILOW, J., NICHOLS, K., MARSHALL, W., KHVOROVA, A., and LINSLEY, P.S. (2006a). Positionspecifc chemical modif cation of siRNAs reduces "off-target" transcript silencing. RNA. 12, 1197-1205.
16. JACKSON, A.L., BURCHARD, J., SCHELTER, J., CHAU, B.N., CLEARY, M., LIM, L., and LINSLEY, P.S. (2006b). Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. RNA. 12, 1179-1187.
17. JUDGE, A., and MACLACHLAN, I. (2008). Overcoming the innate immune response to small interfering RNA. Hum. Gene Ther. 19, 111-124.
18. KLATT, A.R., KLINGER, G., NEUMÜLLER, O., EIDENMÜLLER, B., WAGNER, I., ACHENBACH, T., AIGNER, T., and BARTNIK, E. (2006). TAK1 downregulation reduces IL-1beta induced expression of MMP13, MMP1 and TNF-alpha. Biomed. Pharmacother. 60, 55-61.
19. LIN, X., RUAN, X., ANDERSON, M.G., MCDOWELL, J.A., KROEGER, P.E., FESIK, S.W., and SHEN, Y. (2005). siRNA-medi-ated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res. 33, 4527-4535.
20. MEYLAN, E., TSCHOPP, J., and KARIN, M. (2006). Intracellular pattern recognition receptors in the host response. Nature. 442, 39-44.
21. PIPPIG, D.A., HELLMUTH, J.C., CUI, S., KIRCHHOFER, A., LAMMENS, K., LAMMENS, A., SCHMIDT, A., ROTHENFUSSER, S., and HOPFNER, K.P. (2009). The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA. Nucleic Acids Res. 37, 2014-2025.
22. PURI, N., WANG, X., VARMA, R., BURNETT, C., BEAUCHAMP, L., BATTEN, D.M., YOUNG, M., SULE, V., LATHAM, K., SENDERA, T., ECHEVERRI, C., SACHSE, C., and MAGDALENO, S. (2008). LNA incorporated siRNAs exhibit lower off-target effects compared to 2′-OMethoxy in cell phenotypic assays and microarray analysis. Nucleic Acids Symp. Ser (Oxf). 52, 25-26.
23. ROBBINS, M., JUDGE, A., AMBEGIA, E., CHOI, C., YAWORSKY, E., PALMER, L., MCCLINTOCK, K., and MACLACHLAN, I. (2008). Mis-interpreting the therapeutic effects of small interfering RNA caused by immune stimulation. Hum. Gen Ther. 19, 991-999.
24. ROBBINS, M., JUDGE, A., and MACLACHLAN, I. (2009). siRNA and innate immunity. Oligonucleotides. 19, 89-102.
25. SLEDZ, C.A., HOLKO, M., DE VEER, M.J., SILVERMAN, R.H., and WILLIAMS, B.R. (2003). Activation of the interferon system by short-interfering RNAs. Nat. Cell Biol. 5, 834-839.
26. SLEDZ, C.A., and WILLIAMS, B.R. (2004). RNA interference and double-stranded-RNA-activated pathways. Biochem. Soc. Trans. 32, 952-956.
27. SMYTH, G.K. (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 3, Article3.
28. TSCHUCH, C., SCHULZ, A., PSCHERER, A., WERFT, W., BENNER, A., HOTZ-WAGENBLATT, A., BARRIONUEVO, L.S., LICHTER, P., and MERTENS, D. (2008). Off-target effects of siRNA specif c for GFP. BMC. Mol. Biol. 9, 60-74.
29. TUSCHL, T., ZAMORE, P.D., LEHMANN, R., BARTEL, D.P., and SHARP, P.A. (1999). Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev. 13, 3191-3197.
30. VINCENTI, M.P., and BRINCKERHOFF, C.E. (2002). Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specif c transcription factors. Arthritis Res. 4, 157-164.