Mechanisms and therapeutic applications of immune modulatory oligodeoxynucleotide and oligoribonucleotide ligands for toll-like receptors

Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition

Volumn , Issue , 2007, Pages 747-772

  Vollmer, Jörg ^a   Krieg, Arthur M ^a  

^a PFIZER INC   (United States)

Author keywords

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EID: 77952727502     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (257)

1. Tanaka, T, Chu, CC, and Paul, WE; An antisense oligonucleotide complementary to a sequence in Ig 2b increases γ 2b germline transcripts, stimulates B cell DNA synthesis, and inhibits immunoglobulin secretion; J. Exp. Med.; 175; 597; 1992.
2. Branda, RF, Moore, AL, Mathews, L et al.; Immune stimulation by an antisense oligomer complementary to the rev gene of HIV-1; Biochem. Pharmacol.; 45; 2037; 1993.
3. Pisetsky, DS and Reich, CF; Stimulation of murine lymphocyte proliferation by a phosphorothioate oligonucleotide with antisense activity for herpes simplex virus; Life Sciences; 54; 101; 1993.
4. McIntyre, KW, Lombard-Gillooly, K, Perez, JR et al.; A sense phosphorothioate oligonucleotide directed to the initiation codon of transcription factor NF-κ B p65 causes sequence-specific immune stimulation; Antisense Res. Dev.; 3; 309; 1993.
5. Krieg, AM, Yi, AK, Matson, S et al.; CpG motifs in bacterial DNA trigger direct B-cell activation; Nature; 374; 546; 1995.
6. Krieg, AM; CpG motifs in bacterial DNA and their immune effects; Annu. Rev. Immunol.; 20; 709; 2002.
7. Bird, AP; CpG islands as gene markers in the vertebrate nucleus; Trends Genet.; 3; 342; 1987.
8. Han, J, Zhu, Z, Hsu, C et al.; Selection of antisense oligonucleotides on the basis of genomic frequency of the target sequence; Antisense Res. Dev.; 4; 53; 1994.
9. Hemmi, H, Takeuchi, O, Kawai, T et al.; A Toll-like receptor recognizes bacterial DNA. [In Process Citation]; Nature; 408; 740; 2000.
10. Iwasaki, A and Medzhitov, R; Toll-like receptor control of the adaptive immune responses; Nat. Immunol.; 5; 987; 2004.
11. Pulendran, B; Variegation of the immune response with dendritic cells and pathogen recognition receptors; J. Immunol.; 174; 2457; 2005.
12. Barton, GM, Kagan, JC, and Medzhitov, R; Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA; Nat. Immunol.; 7; 49; 2006.
13. Hemmi, H, Kaisho, T, Takeda, K et al.; The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets; J. Immunol.; 170; 3059; 2003.
14. Vollmer, J, Weeratna, RD, Jurk, M et al.; Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation; Immunology; 113; 212; 2004.
15. Yasuda, K, Yu, P, Kirschning, CJ et al.; Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and-independent pathways; J. Immunol.; 174; 6129; 2005.
16. Ishii, KJ, Coban, C, Kato, H et al.; A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA; Nat. Immunol.; 7; 40; 2006.
17. Okabe, Y, Kawane, K, Akira, S et al.; Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation; J. Exp. Med.; 202; 1333; 2005.
18. Stetson, DB and Medzhitov, R; Recognition of cytosolic DNA activates an IRF3-dependent innate immune response; Immunity; 24; 93; 2006.
19. Spies, B, Hochrein, H, Vabulas, M et al.; Vaccination with plasmid DNA activates dendritic cells via Toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice; J. Immunol.; 171; 5908; 2003.
20. Babiuk, S, Mookherjee, N, Pontarollo, R et al.; TLR9-/-and TLR9+/+ mice display similar immune responses to a DNA vaccine; Immunology; 113; 114; 2004.
21. Tudor, D, Dubuquoy, C, Gaboriau, V et al.; TLR9 pathway is involved in adjuvant effects of plasmid DNA-based vaccines; Vaccine; 23; 1258; 2005.
22. Liu, YJ; IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors; Annu. Rev. Immunol.; 23; 275; 2005.
23. Hayashi, F, Means, TK, and Luster, AD; Toll-like receptors stimulate human neutrophil function; Blood; 102; 2660; 2003.
24. Saikh, KU, Kissner, TL, Sultana, A et al.; Human monocytes infected with Yersinia pestis express cell surface TLR9 and differentiate into dendritic cells; J. Immunol.; 173; 7426; 2004.
25. Siren, J, Pirhonen, J, Julkunen, I et al.; IFN-alpha regulates TLR-dependent gene expression of IFN-alpha, IFN-beta, IL-28, and IL-29; J. Immunol.; 174; 1932; 2005.
26. Gelman, AE, Zhang, J, Choi, Y et al.; Toll-like receptor ligands directly promote activated CD4′ T cell survival; J. Immunol.; 172; 6065; 2004.
27. Li, J, Ma, Z, Tang, ZL et al.; CpG DNA-mediated immune response in pulmonary endothelial cells; Am. J. Physiol. Lung Cell Mol. Physiol.; 287; L552; 2004.
28. Platz, J, Beisswenger, C, Dalpke, A et al.; Microbial DNA induces a host defense reaction of human respiratory epithelial cells; J. Immunol.; 173; 1219; 2004.
29. Pedersen, G, Andresen, L, Matthiessen, MW et al.; Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium; Clin. Exp. Immunol.; 141; 298; 2005.
30. Rachmilewitz, D, Karmeli, F, Shteingart, S et al.; Immunostimulatory oligonucleotides inhibit colonic proinflammatory cytokine production in ulcerative colitis; Inflamm. Bowel. Dis.; 12; 339; 2006.
31. Roda, JM, Parihar, R, and Carson, WE, III; CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells; J. Immunol.; 175; 1619; 2005.
32. Sivori, S, Falco, M, Della, CM et al.; CpG and double-stranded RNA trigger human NK cells by Tolllike receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cells; Proc. Natl. Acad. Sci U.S.A.; 101; 10116; 2004.
33. Sivori, S, Carlomagno, S, Moretta, L et al.; Comparison of different CpG oligodeoxynucleotide classes for their capability to stimulate human NK cells; Eur. J. Immunol.; 2006.
34. Suzuki, Y, Wakita, D, Chamoto, K et al.; Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity; Cancer Res.; 64; 8754; 2004.
35. Romagnani, C, Della, CM, Kohler, S et al.; Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4′ T helper cells and CD4′ CD25hi T regulatory cells; Eur. J. Immunol.; 35; 2452; 2005.
36. Marshall, JD, Heeke, DS, Abbate, C et al.; Induction of interferon-gamma from natural killer cells by immunostimulatory CpG DNA is mediated through plasmacytoid-dendritic-cell-produced interferonalpha and tumour necrosis factor-alpha; Immunology; 117; 38; 2006.
37. Gorski, KS, Waller, EL, Bjornton-Severson, J et al.; Distinct indirect pathways govern human NK-cell activation by TLR-7 and TLR-8 agonists; Int. Immunol.; 18; 1115; 2006.
38. Gerosa, F, Gobbi, A, Zorzi, P et al.; The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions; J. Immunol.; 174; 727; 2005.
39. Hanabuchi, S, Watanabe, N, Wang, YH et al.; Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL); Blood; 107; 3617; 2006.
40. Blackwell, SE and Krieg, AM; CpG-A-induced monocyte IFN-gamma-inducible protein-10 production is regulated by plasmacytoid dendritic cell-derived IFN-alpha; J. Immunol.; 170; 4061; 2003.
41. Jarrossay, D, Napolitani, G, Colonna, M et al.; Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells; Eur. J. Immunol.; 31; 3388; 2001.
42. Komiya, A, Nagase, H, Okugawa, S et al.; Expression and function of toll-like receptors in human basophils; Int. Arch. Allergy Immunol.; 140 Suppl 1; 23; 2006.
43. Chuang, TH and Ulevitch, RJ; Cloning and characterization of a sub-family of human toll-like receptors:hTLR7, hTLR8 and hTLR9 [In Process Citation]; Eur. Cytokine Netw.; 11; 372; 2000.
44. Du, X, Poltorak, A, Wei, Y et al.; Three novel mammalian toll-like receptors: gene structure, expression, and evolution [In Process Citation]; Eur. Cytokine Netw.; 11; 362; 2000.
45. Bsibsi, M, Ravid, R, Gveric, D et al.; Broad expression of Toll-like receptors in the human central nervous system; J. Neuropathol. Exp. Neurol.; 61; 1013; 2002.
46. Nishimura, M and Naito, S; Tissue-specific mRNA expression profiles of human Toll-like receptors and related genes; Biol. Pharm. Bull.; 28; 886; 2005.
47. Zarember, KA and Godowski, PJ; Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines; J. Immunol.; 168; 554; 2002.
48. Hornung, V, Rothenfusser, S, Britsch, S et al.; Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides; J. Immunol.; 168; 4531; 2002.
49. Bekeredjian-Ding, IB, Wagner, M, Hornung, V et al.; Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type I IFN; J. Immunol.; 174; 4043; 2005.
50. Krug, A, Towarowski, A, Britsch, S et al.; Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12; Eur. J. Immunol.; 31; 3026; 2001.
51. Ito, T, Amakawa, R, Kaisho, T et al.; Interferon-alpha and interleukin-12 are induced differentially by Toll-like receptor 7 ligands in human blood dendritic cell subsets; J. Exp. Med.; 195; 1507; 2002.
52. Renn, CN, Sanchez, DJ, Ochoa, MT et al.; TLR activation of Langerhans cell-like dendritic cells triggers an antiviral immune response; J. Immunol.; 177; 298; 2006.
53. Osterlund, P, Veckman, V, Siren, J et al.; Gene expression and antiviral activity of alpha/beta interferons and interleukin-29 in virus-infected human myeloid dendritic cells; J. Virol.; 79; 9608; 2005.
54. Miettinen, M, Sareneva, T, Julkunen, I et al.; IFNs activate toll-like receptor gene expression in viral infections; Genes Immun.; 2; 349; 2001.
55. Kokkinopoulos, I, Jordan, WJ, and Ritter, MA; Toll-like receptor mRNA expression patterns in human dendritic cells and monocytes; Mol. Immunol.; 42; 957; 2005.
56. Peng, G, Guo, Z, Kiniwa, Y et al.; Toll-like receptor 8-mediated reversal of CD4′ regulatory T cell function; Science; 309; 1380; 2005.
57. Sioud, M; Single-stranded small interfering RNA are more immunostimulatory than their doublestranded counterparts: a central role for 2′-hydroxyl uridines in immune responses; Eur. J. Immunol.; 36; 1222; 2006.
58. Bernasconi, NL, Onai, N, and Lanzavecchia, A; A role for Toll-like receptors in acquired immunity:up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells; Blood; 101; 4500; 2003.
59. Caron, G, Duluc, D, Fremaux, I et al.; Direct stimulation of human T cells via TLR5 and TLR7/8:flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4′ T cells; J. Immunol.; 175; 1551; 2005.
60. Jurk, M, Heil, F, Vollmer, J et al.; Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848; Nat. Immunol.; 3; 499; 2002.
61. Edwards, AD, Diebold, SS, Slack, EM et al.; Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines; Eur. J. Immunol.; 33; 827; 2003.
62. Applequist, SE, Wallin, RP, and Ljunggren, HG; Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines; Int. Immunol.; 14; 1065; 2002.
63. Renshaw, M, Rockwell, J, Engleman, C et al.; Cutting edge: impaired Toll-like receptor expression and function in aging; J. Immunol.; 169; 4697; 2002.
64. Cottalorda, A, Verschelde, C, Marcais, A et al.; TLR2 engagement on CD8 T cells lowers the thresholdfor optimal antigen-induced T cell activation; Eur. J. Immunol.; 36; 1684; 2006.
65. Asselin-Paturel, C, Brizard, G, Chemin, K et al.; Type I interferon dependence of plasmacytoid dendritic cell activation and migration; J. Exp. Med.; 201; 1157; 2005.
66. Jung, J, Yi, AK, Zhang, X et al.; Distinct response of human B cell subpopulations in recognition of an innate immune signal, CpG DNA; J. Immunol.; 169; 2368; 2002.
67. Bernasconi, NL, Traggiai, E, and Lanzavecchia, A; Maintenance of serological memory by polyclonal activation of human memory B cells; Science; 298; 2199; 2002.
68. Traggiai, E, Becker, S, Subbarao, K et al.; An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus; Nat. Med.; 10; 871; 2004.
69. Poeck, H, Wagner, M, Battiany, J et al.; Plasmacytoid dendritic cells, antigen and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T cell help; Blood; 103; 3058; 2004.
70. Honda, K, Ohba, Y, Yanai, H et al.; Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction; Nature; 434; 1035; 2005.
71. Latz, E, Schoenemeyer, A, Visintin, A et al.; TLR9 signals after translocating from the ER to CpG DNA in the lysosome; Nat. Immunol.; 5; 190; 2004.
72. Rutz, M, Metzger, J, Gellert, T et al.; Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence-and pH-dependent manner; Eur. J. Immunol.; 34; 2541; 2004.
73. Yi, AK, Tuetken, R, Redford, T et al.; CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species; J. Immunol.; 160; 4755; 1998.
74. Kirsch, JD, Yi, AK, Spitz, DR et al.; Accumulation of glutathione disulfide mediates NF-kappaB activation during immune stimulation with CpG DNA; Antisense Nucleic Acid Drug Dev.; 12; 327; 2002.
75. Ahmad-Nejad, P, Hacker, H, Rutz, M et al.; Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments; Eur. J. Immunol.; 32; 1958; 2002.
76. Hacker, H, Vabulas, RM, Takeuchi, O et al.; Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6; J. Exp. Med.; 192; 595; 2000.
77. Schnare, M, Holtdagger, AC, Takeda, K et al.; Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88; Curr. Biol.; 10; 1139; 2000.
78. Muzio, M, Ni, J, Feng, P et al.; IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling; Science; 278; 1612; 1997.
79. Muzio, M, Natoli, G, Saccani, S et al.; The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6); J. Exp. Med.; 187; 2097; 1998.
80. Hartmann, G and Krieg, AM; Mechanism and function of a newly identified CpG DNA motif in human primary B cells; J. Immunol.; 164; 944; 2000.
81. Yi, AK and Krieg, AM; Rapid induction of mitogen-activated protein kinases by immune stimulatory CpG DNA; J. Immunol.; 161; 4493; 1998.
82. Takeshita, F and Klinman, DM; CpG ODN-mediated regulation of IL-12 p40 transcription; Eur. J. Immunol.; 30; 1967; 2000.
83. Tsujimura, H, Tamura, T, Kong, HJ et al.; Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells; J. Immunol.; 172; 6820; 2004.
84. Choudhury, BK, Wild, JS, Alam, R et al.; In vivo role of p38 mitogen-activated protein kinase in mediating the anti-inflammatory effects of CpG oligodeoxynucleotide in murine asthma; J. Immunol.; 169; 5955; 2002.
85. Yi, AK, Yoon, JG, and Krieg, AM; Convergence of CpG DNA-and BCR-mediated signals at the c-Jun N-terminal kinase and NF-kappaB activation pathways: regulation by mitogen-activated protein kinases; Int. Immunol.; 15; 577; 2003.
86. Yi, AK, Yoon, JG, Yeo, SJ et al.; Role of mitogen-activated protein kinases in CpG DNA-mediated IL-10 and IL-12 production: central role of extracellular signal-regulated kinase in the negative feedback loop of the CpG DNA-mediated Th1 response; J. Immunol.; 168; 4711; 2002.
87. Hacker, H, Mischak, H, Miethke, T et al.; CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation; EMBO J.; 17; 6230; 1998.
88. Manzel, L, Strekowski, L, Ismail, FM et al.; Antagonism of immunostimulatory CpG-oligodeoxynucleotides by 4-aminoquinolines and other weak bases: mechanistic studies; J. Pharmacol. Exp. Ther.; 291; 1337; 1999.
89. Ishii, KJ, Takeshita, F, Gursel, I et al.; Potential role of phosphatidylinositol 3 kinase, rather than DNA-dependent protein kinase, in CpG DNA-induced immune activation; J. Exp. Med.; 196; 269; 2002.
90. Gursel, M, Verthelyi, D, Gursel, I et al.; Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide; J. Leukoc. Biol.; 71; 813; 2002.
91. Krug, A, Rothenfusser, S, Hornung, V et al.; Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells; Eur. J. Immunol.; 31; 2154; 2001.
92. Ballas, ZK, Rasmussen, WL, and Krieg, AM; Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA; J. Immunol.; 157; 1840; 1996.
93. Vollmer, J, Weeratna, R, Payette, P et al.; Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities; Eur. J. Immunol.; 34; 251; 2004.
94. Hartmann, G, Battiany, J, Poeck, H et al.; Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells; Eur. J. Immunol.; 33; 1633; 2003.
95. Guiducci, C, Ott, G, Chan, JH et al.; Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation; J. Exp. Med.; 203; 1999; 2006.
96. Coccia, EM, Severa, M, Giacomini, E et al.; Viral infection and Toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells; Eur. J. Immunol.; 34; 796; 2004.
97. Jurk, M, Schulte, B, Kritzler, A et al.; Oligonucleotide-induced production of new antiviral cytokines IL-28 and IL-29 by human immune cells is CpG-dependent; Gordon Research Conference Immunochemistry & Immunobiology; 2005.
98. Jurk, M, Schulte, B, Kritzler, A et al.; C-Class CpG ODN: sequence requirements and characterization of immunostimulatory activities on mRNA level; Immunobiology; 209; 141; 2004.
99. Kranzer, K, Bauer, M, Lipford, GB et al.; CpG-oligodeoxynucleotides enhance T-cell receptor-triggered interferon-γ production and up-regulation of CD69 via induction of antigen-presenting cell-derived interferon type I and interleukin-12; Immunology; 99; 170; 2000.
100. Marschner, A, Rothenfusser, S, Hornung, V et al.; CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells; Eur. J. Immunol.; 35; 2347; 2005.
101. Rothenfusser, S, Hornung, V, Ayyoub, M et al.; CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8+ T-cell responses in vitro; Blood; 103; 2162; 2004.
102. Rothenfusser, S, Hornung, V, Krug, A et al.; Distinct CpG oligonucleotide sequences activate human gamma delta T cells via interferon-alpha/-beta; Eur. J. Immunol.; 31; 3525; 2001.
103. Montoya, CJ, Jie, HB, Al Harthi, L et al.; Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells; J. Immunol.; 177; 1028; 2006.
104. Kemp, TJ, Elzey, BD, and Griffith, TS; Plasmacytoid dendritic cell-derived IFN-alpha induces TNF-related apoptosis-inducing ligand/apo-2L-mediated antitumor activity by human monocytes following CpG oligodeoxynucleotide stimulation; J. Immunol.; 171; 212; 2003.
105. Matikainen, S, Paananen, A, Miettinen, M et al.; IFN-alpha and IL-18 synergistically enhance IFN-gamma production in human NK cells: differential regulation of Stat4 activation and IFN-gamma gene expression by IFN-alpha and IL-12; Eur. J. Immunol.; 31; 2236; 2001.
106. Micallef, MJ, Yoshida, K, Kawai, S et al.; In vivo antitumor effects of murine interferon-gamma-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites; Cancer Immunol. Immunother.; 43; 361; 1997.
107. Kato, A, Homma, T, Batchelor, J et al.; Interferon-alpha/beta receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006; BMC. Immunol.; 4; 8; 2003.
108. Vollmer, J, Jurk, M, Samulowitz, U et al.; CpG oligodeoxynucleotides stimulate IFN-gammainducible protein-10 production in human B cells; J. Endotoxin. Res.; 10; 431; 2004.
109. Hartmann, G and Krieg, AM; CpG DNA and LPS induce distinct patterns of activation in human monocytes; Gene Ther.; 6; 893; 1999.
110. Hartmann, G, Weeratna, RD, Ballas, ZK et al.; Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo; J. Immunol.; 164; 1617; 2000.
111. Krieg, AM, Efler, SM, Wittpoth, M et al.; Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist; J. Immunother.; 27; 460; 2004.
112. Friedberg, JW, Kim, H, McCauley, M et al.; Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-alpha/betainducible gene expression, without significant toxicity; Blood; 105; 489; 2005.
113. Vollmer, J; TLR9 in health and disease; Int. Rev. Immunol.; 25; 155; 2006.
114. Redford, TW, Yi, AK, Ward, CT et al.; Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides; J. Immunol.; 161; 3930; 1998.
115. Duramad, O, Fearon, KL, Chan, JH et al.; IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences; Blood; 102; 4487; 2003.
116. Gary-Gouy, H, Lebon, P, and Dalloul, AH; Type I interferon production by plasmacytoid dendritic cells and monocytes is triggered by viruses, but the level of production is controlled by distinct cytokines; J. Interferon Cytokine Res.; 22; 653; 2002.
117. Vicari, AP, Chiodoni, C, Vaure, C et al.; Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody; J. Exp. Med.; 196; 541; 2002.
118. Lee, KW, Lee, Y, Kim, DS et al.; Direct role of NF-kappaB activation in Toll-like receptor-triggered HLA-DRA expression; Eur. J. Immunol.; 36; 1254; 2006.
119. Hartmann, G, Weiner, GJ, and Krieg, AM; CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells; Proc. Natl. Acad. Sci. U.S.A.; 96; 9305; 1999.
120. Ashman, RF, Goeken, JA, Drahos, J et al.; Sequence requirements for oligodeoxyribonucleotide inhibitory activity; Int. Immunol.; 17; 411; 2005.
121. Stunz, LL, Lenert, P, Peckham, D et al.; Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells; Eur. J. Immunol.; 32; 1212; 2002.
122. Lenert, P, Stunz, LL, Yi, AK et al.; CpG stimulation of primary mouse B cells is blocked by inhibitory oligodeoxyribonucleotides at a site proximal to NF-kB activation; Antisense Nucleic Acid Drug Dev.; 11; 247; 2001.
123. Vollmer, J, Tluk, S, Schmitz, C et al.; Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8; J. Exp. Med.; 202; 1575; 2005.
124. Barrat, FJ, Meeker, T, Gregorio, J et al.; Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus; J. Exp. Med.; 202; 1131; 2005.
125. Marshak-Rothstein, A, Busconi, L, Lau, CM et al.; Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells; J. Endotoxin. Res.; 10; 247; 2004.
126. Leadbetter, EA, Rifkin, IR, Hohlbaum, AM et al.; Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors; Nature; 416; 603; 2002.
127. Lau, CM, Broughton, C, Tabor, AS et al.; RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement; J. Exp. Med.; 202; 1171; 2005.
128. Dong, L, Ito, S, Ishii, KJ et al.; Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB × NZW mice; Arthritis Rheum.; 52; 651; 2005.
129. Dong, L, Ito, S, Ishii, KJ et al.; Suppressive oligonucleotides protect against collagen-induced arthritis in mice; Arthritis Rheum.; 50; 1686; 2004.
130. Vollmer, J; CpG motifs to modulate innate and adaptive immune responses; Int. Rev. Immunol.; 25; 125; 2006.
131. Yu, D, Zhao, Q, Kandimalla, ER et al.; Accessible 5′-end of CpG-containing phosphorothioate oligodeoxynucleotides is essential for immunostimulatory activity; Bioorg. Med. Chem. Lett.; 10; 2585; 2000.
132. Vollmer, J, Janosch, A, Laucht, M et al.; Highly immunostimulatory CpG-free oligodeoxynucleotides for activation of human leukocytes; Antisense Nucleic Acid Drug Dev.; 12; 165; 2002.
133. Liang, H, Nishioka, Y, Reich, CF et al.; Activation of human B cells by phosphorothioate oligodeoxynucleotides; J. Clin. Invest.; 98; 1119; 1996.
134. Sester, DP, Naik, S, Beasley, SJ et al.; Phosphorothioate backbone modification modulates macrophage activation by CpG DNA; J. Immunol.; 165; 4165; 2000.
135. Krieg, AM, Guga, P, and Stec, W; P-chirality-dependent immune activation by phosphorothioate CpG oligodeoxynucleotides; Oligonucleotides; 13; 491; 2003.
136. Yu, D, Kandimalla, ER, Roskey, A et al.; Stereo-enriched phosphorothioate oligodeoxynucleotides:synthesis, biophysical and biological properties [In Process Citation]; Bioorg. Med. Chem.; 8; 275; 2000.
137. Agrawal, S and Kandimalla, ER; Medicinal chemistry and therapeutic potential of CpG DNA; Trends Mol. Med.; 8; 114; 2002.
138. Jurk, M, Kritzler, A, Debelak, H et al.; Structure-activity relationship studies on the immune stimulatory effects of base-modified CpG Toll-like receptor 9 agonists; ChemMedChem.; 1; 1007; 2006.
139. Uhlmann, E and Vollmer, J; Recent advances in the development of immunostimulatory oligonucleotides; Curr. Opin. Drug Discov. Devel.; 6; 204; 2003.
140. Zhao, Q, Temsamani, J, Iadarola, PL et al.; Effect of different chemically modified oligodeoxynucleotides on immune stimulation; Biochem. Pharmacol.; 51; 173; 1996.
141. Vollmer, J, Jepsen, JS, Uhlmann, E et al.; Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA); Oligonucleotides; 14; 23; 2004.
142. Henry, S, Stecker, K, Brooks, D et al.; Chemically modified oligonucleotides exhibit decreased immune stimulation in mice; J. Pharmacol. Exp. Ther.; 292; 468; 2000.
143. Zhao, Q, Yu, D, and Agrawal, S; Immunostimulatory activity of CpG containing phosphorothioate oligodeoxynucleotide is modulated by modification of a single deoxynucleoside; Bioorg. Med. Chem. Lett.; 10; 1051; 2000.
144. Zhao, Q, Yu, D, and Agrawal, S; Site of chemical modifications in CpG containing phosphorothioate oligodeoxynucleotide modulates its immunostimulatory activity; Bioorg. Med. Chem. Lett.; 9; 3453; 1999.
145. Verthelyi, D, Ishii, KJ, Gursel, M et al.; Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs; J. Immunol.; 166; 2372; 2001.
146. Vollmer, J, Weeratna, RD, Jurk, M et al.; Impact of modifications of heterocyclic bases in CpG dinucleotides on their immune-modulatory activity; J. Leukoc. Biol.; 76; 585; 2004.
147. Marshall, JD, Fearon, K, Abbate, C et al.; Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions; J. Leukoc. Biol.; 73; 781; 2003.
148. Yasuda, K, Rutz, M, Schlatter, B et al.; CpG motif-independent activation of TLR9 upon endosomal translocation of “natural” phosphodiester DNA; Eur. J. Immunol.; 36; 431; 2006.
149. McCluskie, MJ and Davis, HL; Oral, intrarectal and intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants [In Process Citation]; Vaccine; 19; 413; 2001.
150. Ho, PP, Fontoura, P, Ruiz, PJ et al.; An immunomodulatory GpG oligonucleotide for the treatment of autoimmunity via the innate and adaptive immune systems; J. Immunol.; 171; 4920; 2003.
151. Gursel, I, Gursel, M, Yamada, H et al.; Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation; J. Immunol.; 171; 1393; 2003.
152. Elkins, KL, Rhinehart-Jones, TR, Stibitz, S et al.; Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria; J. Immunol.; 162; 2291; 1999.
153. Gramzinski, RA, Doolan, DL, Sedegah, M et al.; Interleukin-12-and γ interferon-dependent protection against malaria conferred by CpG oligodeoxynucleotide in mice; Infect. Immun.; 69; 1643; 2001.
154. Zimmermann, S, Egeter, O, Hausmann, S et al.; CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis; J. Immunol.; 160; 3627; 1998.
155. Krieg, AM, Love-Homan, L, Yi, AK et al.; CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge; J. Immunol.; 161; 2428; 1998.
156. Klinman, DM, Conover, J, and Coban, C; Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection; Infect. Immun.; 67; 5658; 1999.
157. Klinman, DM, Verthelyi, D, Takeshita, F et al.; Immune recognition of foreign DNA: a cure for bioterrorism?; Immunity; 11; 123; 1999.
158. Rees, DG, Gates, AJ, Green, M et al.; CpG-DNA protects against a lethal orthopoxvirus infection in a murine model; Antiviral Res.; 65; 87; 2005.
159. Deng, JC, Moore, TA, Newstead, MW et al.; CpG oligodeoxynucleotides stimulate protective innate immunity against pulmonary Klebsiella infection; J. Immunol.; 173; 5148; 2004.
160. Ray, NB and Krieg, AM; Oral pretreatment of mice with CpG DNA reduces susceptibility to oral or intraperitoneal challenge with virulent Listeria monocytogenes; Infect. Immun.; 71; 4398; 2003.
161. Klinman, DM; Immunotherapeutic uses of CpG oligodeoxynucleotides; Nat. Rev. Immunol.; 4; 249; 2004.
162. Weighardt, H, Feterowski, C, Veit, M et al.; Increased resistance against acute polymicrobial sepsis in mice challenged with immunostimulatory CpG oligodeoxynucleotides is related to an enhanced innate effector cell response [In Process Citation]; J. Immunol.; 165; 4537; 2000.
163. Pyles, RB, Higgins, D, Chalk, C et al.; Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection; J. Virol.; 76; 11387; 2002.
164. Ashkar, AA, Bauer, S, Mitchell, WJ et al.; Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication, but not entry, of herpes simplex virus type 2; J. Virol.; 77; 8948; 2003.
165. Walker, PS, Scharton-Kersten, T, Krieg, AM et al.; Immunostimulatory oligodeoxynucleotides promote protective immunity and provide systemic therapy for leishmaniasis via IL-12-and IFN-γ-dependent mechanisms; Proc. Natl. Acad. Sci. U.S.A.; 96; 6970; 1999.
166. Cho, JY, Miller, M, Baek, KJ et al.; Immunostimulatory DNA sequences inhibit respiratory syncytial viral load, airway inflammation, and mucus secretion; J. Allergy Clin. Immunol.; 108; 697; 2001.
167. Juffermans, NP, Leemans, JC, Florquin, S et al.; CpG oligodeoxynucleotides enhance host defense during murine tuberculosis; Infect. Immun.; 70; 147; 2002.
168. Olbrich, AR, Schimmer, S, Heeg, K et al.; Effective postexposure treatment of retrovirus-induced disease with immunostimulatory DNA containing CpG motifs; J. Virol.; 76; 11397; 2002.
169. Freidag, BL, Melton, GB, Collins, F et al.; CpG oligodeoxynucleotides and interleukin-12 improve the efficacy of Mycobacterium bovis BCG vaccination in mice challenged with M. tuberculosis; Infect. Immun.; 68; 2948; 2000.
170. Ramirez-Pineda, JR, Frohlich, A, Berberich, C et al.; Dendritic cells (DC) activated by CpG DNA ex vivo are potent inducers of host resistance to an intracellular pathogen that is independent of IL-12 derived from the immunizing DC; J. Immunol.; 172; 6281; 2004.
171. Ishii, KJ, Ito, S, Tamura, T et al.; CpG-activated Thy1.2′ dendritic cells protect against lethal Listeria monocytogenes infection; Eur. J. Immunol.; 35; 2397; 2005.
172. Lugo-Villarino, G, Ito, S, Klinman, DM et al.; The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells; Proc. Natl. Acad. Sci. U.S.A.; 102; 13248; 2005.
173. Shen, H and Iwasaki, A; A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN-based vaginal microbicide; J. Clin. Invest.; 116; 2237; 2006.
174. Kuwajima, S, Sato, T, Ishida, K et al.; Interleukin 15-dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation; Nat. Immunol.; 7; 740; 2006.
175. Isogawa, M, Robek, MD, Furuichi, Y et al.; Toll-like receptor signaling inhibits hepatitis B virus replication in vivo; J. Virol.; 79; 7269; 2005.
176. Rehermann, B and Nascimbeni, M; Immunology of hepatitis B virus and hepatitis C virus infection; Nat. Rev. Immunol.; 5; 215; 2005.
177. McHutchison, JG, Bacon, BR, Gordon, SC et al.; Relationships of HCV RNA responses to CPG 10101, a TLR9 agonist: pharmacodynamics & patient characteristics; AASLD; 2005.
178. Vallin, H, Perers, A, Alm, GV et al.; Anti-double-stranded DNA antibodies and immunostimulatory plasmid DNA in combination mimic the endogenous IFN-α inducer in systemic lupus erythematosus; J. Immunol.; 163; 6306; 1999.
179. Yi, AK, Chang, M, Peckham, DW et al.; CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous apoptosis and promote cell cycle entry [published erratum appears in J. Immunol. 1999 Jul 15; 163(2): 1093]; J. Immunol.; 160; 5898; 1998.
180. Davis, HL, Weeratna, R, Waldschmidt, TJ et al.; CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen [published erratum appears in J. Immunol. 1999 Mar 1; 162(5): 3103]; J. Immunol.; 160; 870; 1998.
181. Liu, N, Ohnishi, N, Ni, L et al.; CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells; Nat. Immunol.; 4; 687; 2003.
182. He, B, Qiao, X, and Cerutti, A; CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10; J. Immunol.; 173; 4479; 2004.
183. Lipford, GB, Sparwasser, T, Zimmermann, S et al.; CpG-DNA-mediated transient lymphadenopathy is associated with a state of Th1 predisposition to antigen-driven responses; J. Immunol.; 165; 1228; 2000.
184. Sparwasser, T, Vabulas, RM, Villmow, B et al.; Bacterial CpG-DNA activates dendritic cells in vivo:T helper cell-independent cytotoxic T cell responses to soluble proteins; Eur. J. Immunol.; 30; 3591; 2000.
185. Krieg, AM and Davis, HL; Enhancing vaccines with immune stimulatory CpG DNA; Curr. Opin. Mol. Ther.; 3; 15; 2001.
186. Cooper, CL, Davis, H, Morris, ML et al.; CpG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study; J. Clin. Immunol.; 24; 693; 2004.
187. Halperin, SA, Van Nest, G, Smith, B et al.; A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant; Vaccine; 21; 2461; 2003.
188. Siegrist, CA, Pihlgren, M, Tougne, C et al.; Co-administration of CpG oligonucleotides enhances the late affinity maturation process of human anti-hepatitis B vaccine response; Vaccine; 23; 615; 2004.
189. Rynkiewicz, D, Rathkopf, M, Ransom, J et al.; Marked Enhancement of Antibody Response to Anthrax Vaccine Adsorbed with CPG 7909 in Healthy Volunteers; ICAAC; 2005.
190. Cooper, CL, Davis, HL, Angel, JB et al.; CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults; AIDS; 19; 1473; 2005.
191. Weeratna, R, Comanita, L, and Davis, HL; CPG ODN allows lower dose of antigen against hepatitis B surface antigen in BALB/c mice; Immunol. Cell Biol.; 81; 59; 2003.
192. Cooper, CL, Davis, H, Morris, ML et al.; Safety and immunogenicity of CpG 7909 injection as an adjuvant to Fluarix Influenza vaccine; Vaccine; 22; 3136; 2004.
193. Krieg, AM; Antitumor applications of stimulating Toll-like receptor 9 with CpG oligodeoxynucleotides; Curr. Oncol. Rep.; 6; 88; 2004.
194. Link, B, Ballas, Z, Weisdorf, D et al.; Oligodeoxynucleotide CPG 7909 delivered as intravenous infusion demonstrates immunologic modulation in patients with previously treated non-Hodgkin’s lymphoma; J. Immunother.; 2006.
195. Weigel, BJ, Rodeberg, DA, Krieg, AM et al.; CpG oligodeoxynucleotides potentiate the antitumor effects of chemotherapy or tumor resection in an orthotopic murine model of rhabdomyosarcoma; Clin. Cancer Res.; 9; 3105; 2003.
196. Balsari, A, Tortoreto, M, Besusso, D et al.; Combination of a CpG-oligodeoxynucleotide and a topoisomerase I inhibitor in the therapy of human tumour xenografts; Eur. J. Cancer; 40; 1275; 2004.
197. Wang, XS, Sheng, Z, Ruan, YB et al.; CpG oligodeoxynucleotides inhibit tumor growth and reverse the immunosuppression caused by the therapy with 5-fluorouracil in murine hepatoma; World J. Gastroenterol.; 11; 1220; 2005.
198. Manegold, C, Leichman, G, Gravenor, D et al.; Addition of PF-3512676 (CpG 7909) to a taxane/platinum regimen for first-line treatment of unresectable non-small cell lung cancer (NSCLC) improves objective response-Phase II clinical trial; Eur. J. Cancer; 3; 326; 2005.
199. van Ojik, H, Kruit, W, Portielje, J et al.; Phase I/II study with CpG 7909 as adjuvant to vaccination with MAGA-3 protein in patients with MAGE-3 positive tumors; Ann. Oncol.; 13; 157; 2002.
200. Speiser, DE, Lienard, D, Rufer, N et al.; Rapid and strong human CD8(+) T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909; J. Clin. Invest.; 115; 739; 2005.
201. Kline, JN, Waldschmidt, TJ, Businga, TR et al.; Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma; J. Immunol.; 160; 2555; 1998.
202. Jain, VV, Kitagaki, K, Businga, T et al.; CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma; J. Allergy Clin. Immunol.; 110; 867; 2002.
203. Creticos, PS, Eiden, JJ, and et al.; Immunotherapy with immunostimulatory oligonucleotides linked to purified ragweed Amb a 1 allergen: effects on antibody production, nasal allergen provocation, and ragweed seasonal rhinitis; J. Allergy Clin. Immunol.; 109; 742; 2002.
204. Simons, FE, Shikishima, Y, Van Nest, G et al.; Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA; J. Allergy Clin. Immunol.; 113; 1144; 2004.
205. Racila, DM and Kline, JN; Perspectives in asthma: molecular use of microbial products in asthma prevention and treatment; J. Allergy Clin. Immunol.; 116; 1202; 2005.
206. Hayashi, T, Beck, L, Rossetto, C et al.; Inhibition of experimental asthma by indoleamine 2,3-dioxygenase; J. Clin. Invest.; 114; 270; 2004.
207. Jain, VV, Businga, TR, Kitagaki, K et al.; Mucosal immunotherapy with CpG oligodeoxynucleotides reverses a murine model of chronic asthma induced by repeated antigen exposure; Am. J. Physiol. Lung Cell Mol. Physiol.; 285; L1137; 2003.
208. Fanucchi, MV, Schelegle, ES, Baker, GL et al.; Immunostimulatory oligonucleotides attenuate airways remodelling in allergic monkeys; Am. J. Respir. Crit. Care Med.; 170; 1153; 2004.
209. Gauvreau, GM, Hessel, EM, Boulet, LP et al.; Immunostimulatory sequences regulate interferoninducible genes but not allergic airway responses; Am. J. Respir. Crit. Care Med.; 2006.
210. Viglianti, GA, Lau, CM, Hanley, TM et al.; Activation of autoreactive B cells by CpG dsDNA; Immunity; 19; 837; 2003.
211. Boule, MW, Broughton, C, Mackay, F et al.; Toll-like receptor 9-dependent and-independent dendritic cell activation by chromatin-immunoglobulin G complexes; J. Exp. Med.; 199; 1631; 2004.
212. Christensen, SR, Kashgarian, M, Alexopoulou, L et al.; Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus; J. Exp. Med.; 202; 321; 2005.
213. Means, TK, Latz, E, Hayashi, F et al.; Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9; J. Clin. Invest.; 115; 407; 2005.
214. Lovgren, T, Eloranta, ML, Kastner, B et al.; Induction of interferon-alpha by immune complexes or liposomes containing systemic lupus erythematosus autoantigen-and Sjogren’s syndrome autoantigen-associated RNA; Arthritis Rheum.; 54; 1917; 2006.
215. Levin, AA, Henry, S, Monteith, D, and Templin, MV; Toxicity of antisense oligonucleotides; in Antisense Drug Technology; Crooke, ST, Ed., Marcel Dekker, New York; 201; 2001.
216. Levin, AA; A review of the issues in the pharmacokinetics and toxicology of phosphorothioate antisense oligonucleotides; Biochim. Biophys. Acta; 1489; 69; 1999.
217. Monteith, DK and Levin, AA; Synthetic oligonucleotides: the development of antisense therapeutics; Toxicol. Pathol.; 27; 8; 1999.
218. Henry, SP, Taylor, J, Midgley, L et al.; Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1 mice; Antisense Nucleic Acid Drug Dev.; 7; 473; 1997.
219. Sparwasser, T, Miethke, T, Lipford, G et al.; Bacterial DNA causes septic shock [letter]; Nature; 386; 336; 1997.
220. Hasegawa, K and Hayashi, T; Synthetic CpG oligodeoxynucleotides accelerate the development of lupus nephritis during preactive phase in NZB × NZWF1 mice; Lupus; 12; 838; 2003.
221. Ichikawa, HT, Williams, LP, and Segal, BM; Activation of APCs through CD40 or Toll-like receptor 9 overcomes tolerance and precipitates autoimmune disease; J. Immunol.; 169; 2781; 2002.
222. Obermeier, F, Dunger, N, Deml, L et al.; CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice; Eur. J. Immunol.; 32; 2084; 2002.
223. Ronaghy, A, Prakken, BJ, Takabayashi, K et al.; Immunostimulatory DNA sequences influence the course of adjuvant arthritis; J. Immunol.; 168; 51; 2002.
224. Boccaccio, GL, Mor, F, and Steinman, L; Non-coding plasmid DNA induces IFN-γ in vivo and suppresses autoimmune encephalomyelitis; Int. Immunol.; 11; 289; 1999.
225. Quintana, FJ, Rotem, A, Carmi, P et al.; Vaccination with empty plasmid DNA or CpG oligonucleotide inhibits diabetes in nonobese diabetic mice: modulation of spontaneous 60-kDa heat shock protein autoimmunity; J. Immunol.; 165; 6148; 2000.
226. Katakura, K, Lee, J, Rachmilewitz, D et al.; Toll-like receptor 9-induced type I IFN protects mice from experimental colitis; J. Clin. Invest.; 115; 695; 2005.
227. Roach, JC, Glusman, G, Rowen, L et al.; The evolution of vertebrate Toll-like receptors; Proc. Natl. Acad. Sci. U.S.A.; 102; 9577; 2005.
228. Wagner, H; The immunobiology of the TLR9 subfamily; Trends Immunol.; 25; 381; 2004.
229. Lund, JM, Alexopoulou, L, Sato, A et al.; Recognition of single-stranded RNA viruses by Toll-like receptor 7; Proc. Natl. Acad. Sci. U.S.A.; 101; 5598; 2004.
230. Beignon, AS, McKenna, K, Skoberne, M et al.; Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions; J. Clin. Invest.; 2005.
231. Diebold, SS, Kaisho, T, Hemmi, H et al.; Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA; Science; 303; 1529; 2004.
232. Melchjorsen, J, Jensen, SB, Malmgaard, L et al.; Activation of innate defense against a paramyxovirus is mediated by RIG-I and TLR7 and TLR8 in a cell-type-specific manner; J. Virol.; 79; 12944; 2005.
233. Hemmi, H, Kaisho, T, Takeuchi, O et al.; Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway; Nat. Immunol.; 3; 196; 2002.
234. Heil, F, Ahmad-Nejad, P, Hemmi, H et al.; The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily; Eur. J. Immunol.; 33; 2987; 2003.
235. Gibson, SJ, Lindh, JM, Riter, TR et al.; Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod; Cell Immunol.; 218; 74; 2002.
236. Heil, F, Hemmi, H, Hochrein, H et al.; Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8; Science; 303; 1526; 2004.
237. Judge, AD, Sood, V, Shaw, JR et al.; Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA; Nat. Biotechnol.; 23; 457; 2005.
238. Hornung, V, Guenthner-Biller, M, Bourquin, C et al.; Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7; Nat. Med.; 11; 263; 2005.
239. Sioud, M; Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization; J. Mol. Biol.; 348; 1079; 2005.
240. Probst, J, Brechtel, S, Scheel, B et al.; Characterization of the ribonuclease activity on the skin surface; Genet. Vaccines. Ther.; 4; 4; 2006.
241. Nishiya, T and DeFranco, AL; Ligand-regulated chimeric receptor approach reveals distinctive subcellular localization and signaling properties of the Toll-like receptors; J. Biol. Chem.; 279; 19008; 2004.
242. Nishiya, T, Kajita, E, Miwa, S et al.; TLR3 and TLR7 are targeted to the same intracellular compartments by distinct regulatory elements; J. Biol. Chem.; 2005.
243. Kariko, K, Buckstein, M, Ni, H et al.; Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA; Immunity; 23; 165; 2005.
244. Scheel, B, Braedel, S, Probst, J et al.; Immunostimulating capacities of stabilized RNA molecules; Eur. J. Immunol.; 34; 537; 2004.
245. Forsbach, A, Montino, C, Muller, C et al.; Identification of ssRNA sequences that stimulate innate immunity through TLRs; Clin. Immunol.; Supplement 1, 2005; 2005.
246. Gorden, KB, Gorski, KS, Gibson, SJ et al.; Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8; J. Immunol.; 174; 1259; 2005.
247. Nemorin, JG, Lampron, C, McCluskie, M et al.; Adjuvant activity of ssRNA in Hepatitis B vaccine; First Meeting of the Oligonucleotide Therapeutics Society 2005; 2005.
248. Bekeredjian-Ding, I, Roth, SI, Gilles, S et al.; T cell-independent, TLR-induced IL-12p70 production in primary human monocytes; J. Immunol.; 176; 7438; 2006.
249. Riedl, P, Stober, D, Oehninger, C et al.; Priming Th1 immunity to viral core particles is facilitated by trace amounts of RNA bound to its arginine-rich domain; J. Immunol.; 168; 4951; 2002.
250. Westwood, A, Elvin, SJ, Healey, GD et al.; Immunological responses after immunisation of mice with microparticles containing antigen and single stranded RNA (polyuridylic acid); Vaccine; 24; 1736; 2006.
251. Jacobs, BL and Langland, JO; When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA; Virology; 219; 339; 1996.
252. Loseke, S, Grage-Griebenow, E, Heine, H et al.; In vitro-generated viral double-stranded RNA in contrast to polyinosinic:polycytidylic acid induces interferon-alpha in human plasmacytoid dendritic cells; Scand. J. Immunol.; 63; 264; 2006.
253. Alexopoulou, L, Holt, AC, Medzhitov, R et al.; Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3; Nature; 413; 732; 2001.
254. Yoneyama, M, Kikuchi, M, Natsukawa, T et al.; The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses; Nat. Immunol.; 5; 730; 2004.
255. Yoneyama, M, Kikuchi, M, Matsumoto, K et al.; Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity; J. Immunol.; 175; 2851; 2005.
256. Meylan, E, Curran, J, Hofmann, K et al.; Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus; Nature; 437; 1167; 2005.
257. Balachandran, S, Roberts, PC, Brown, LE et al.; Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection; Immunity; 13; 129; 2000.