Staying on message: Design principles for controlling nonspecific responses to siRNA

FEBS Journal

Volumn 277, Issue 23, 2010, Pages 4828-4836

  Samuel Abraham, Shirley ^a   Leonard, Joshua N ^a,b  

^a Northwestern University   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Innate immunity; OAS1; Off target; RIG I; RNA interference; RNAi; Short interfering RNA; SiRNA; TLR; Toll like receptors

Indexed keywords

SMALL INTERFERING RNA; TOLL LIKE RECEPTOR;

ANTIGEN RECOGNITION; DRUG DESIGN; GENE DELIVERY SYSTEM; HUMAN; IMMUNOREACTIVITY; IMMUNOSTIMULATION; NONHUMAN; NUCLEIC ACID BASE SUBSTITUTION; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REVIEW; RNA INTERFERENCE; RNA PROCESSING; RNA SEQUENCE; RNA STRUCTURE;

ANIMALS; BASE SEQUENCE; DRUG DELIVERY SYSTEMS; DRUG DESIGN; GENE KNOCKDOWN TECHNIQUES; GENETIC ENGINEERING; HUMANS; IMMUNITY, INNATE; RNA, SMALL INTERFERING;

EID: 78449299462     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2010.07905.x     Document Type: Review

References (56)

1. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE & Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811.
2. Wianny F & Zernicka-Goetz M (2000) Specific interference with gene function by double-stranded RNA in early mouse development. Nat Cell Biol 2, 70-75.
3. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K & Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494-498.
4. Castanotto D & Rossi JJ (2009) The promises and pitfalls of RNA-interference-based therapeutics. Nature 457, 426-433.
5. Kleinman ME, Yamada K, Takeda A, Chandrasekaran V, Nozaki M, Baffi JZ, Albuquerque RJ, Yamasaki S, Itaya M, Pan Y et al. (2008) Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452, 591-597.
6. Cho WG, Albuquerque RJ, Kleinman ME, Tarallo V, Greco A, Nozaki M, Green MG, Baffi JZ, Ambati BK, De Falco M et al. (2009) Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth. Proc Natl Acad Sci USA 106, 7137-7142.
7. Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD & Ribas A (2010) Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464, 1067-1070.
8. Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, Breen W, Hartsough K, Machemer L, Radka S, Jadhav V et al. (2005) Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23, 1002-1007.
9. Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya SS, Kirschnek S, Gaffal E, Landsberg J, Hellmuth J et al. (2008) 5'-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat Med 14, 1256-1263.
10. Lampson GP, Tytell AA, Field AK, Nemes MM & Hilleman MR (1967) Inducers of interferon and host resistance. I. Double-stranded RNA from extracts of Penicillium funiculosum. Proc Natl Acad Sci USA 58, 782-789.
11. Williams BR (2001) Signal integration via PKR. Sci STKE 2001, re2.
12. Manche L, Green SR, Schmedt C & Mathews MB (1992) Interactions between double-stranded RNA regulators and the protein kinase DAI. Mol Cell Biol 12, 5238-5248.
13. Marques JT, Devosse T, Wang D, Zamanian-Daryoush M, Serbinowski P, Hartmann R, Fujita T, Behlke MA & Williams BR (2006) A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells. Nat Biotechnol 24, 559-565.
14. Zhang Z, Weinschenk T, Guo K & Schluesener HJ (2006) siRNA binding proteins of microglial cells: PKR is an unanticipated ligand. J Cell Biochem 97, 1217-1229.
15. Minks MA, Benvin S, Maroney PA & Baglioni C (1979) Metabolic stability of 2' 5'oligo (A) and activity of 2' 5'oligo (A)-dependent endonuclease in extracts of interferon-treated and control HeLa cells. Nucleic Acids Res 6, 767-780.
16. Malathi K, Dong B, Gale M Jr & Silverman RH (2007) Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448, 816-819.
17. Kodym R, Kodym E & Story MD (2009) 2'-5'-Oligoadenylate synthetase is activated by a specific RNA sequence motif. Biochem Biophys Res Commun 388, 317-322.
18. Kariko K, Bhuyan P, Capodici J & Weissman D (2004) Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through toll-like receptor 3. J Immunol 172, 6545-6549.
19. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H & Bauer S (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303, 1526-1529.
20. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, Noronha A, Manoharan M, Akira S, De Fougerolles A et al. (2005) Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11, 263-270.
21. Gantier MP, Tong S, Behlke MA, Xu D, Phipps S, Foster PS & Williams BR (2008) TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages. J Immunol 180, 2117-2124.
22. Forsbach A, Nemorin JG, Montino C, Muller C, Samulowitz U, Vicari AP, Jurk M, Mutwiri GK, Krieg AM, Lipford GB et al. (2008) Identification of RNA sequence motifs stimulating sequence-specific TLR8-dependent immune responses. J Immunol 180, 3729-3738.
23. Sioud M (2006) Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: a central role for 2'-hydroxyl uridines in immune responses. Eur J Immunol 36, 1222-1230.
24. Kumar H, Kawai T & Akira S (2009) Pathogen recognition in the innate immune response. Biochem J 420, 1-16.
25. Gorden KB, Gorski KS, Gibson SJ, Kedl RM, Kieper WC, Qiu X, Tomai MA, Alkan SS & Vasilakos JP (2005) Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J Immunol 174, 1259-1268.
26. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K et al. (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301, 640-643.
27. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ et al. (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441, 101-105.
28. Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann KK, Schlee M et al. (2006) 5'-Triphosphate RNA is the ligand for RIG-I. Science 314, 994-997.
29. Walton SP, Wu M, Gredell JA & Chan C (2010) Designing highly active siRNAs for therapeutic applications. FEBS J 277, 4806-4813.
30. Diebold SS, Massacrier C, Akira S, Paturel C, Morel Y & Reis e Sousa C (2006) Nucleic acid agonists for Toll-like receptor 7 are defined by the presence of uridine ribonucleotides. Eur J Immunol 36, 3256-3267.
31. Layzer JM, McCaffrey AP, Tanner AK, Huang Z, Kay MA & Sullenger BA (2004) In vivo activity of nuclease-resistant siRNAs. RNA 10, 766-771.
32. Sledz CA, Holko M, De Veer MJ, Silverman RH & Williams BR (2003) Activation of the interferon system by short-interfering RNAs. Nat Cell Biol 5, 834-839.
33. Leonard JN, Ghirlando R, Askins J, Bell JK, Margulies DH, Davies DR & Segal DM (2008) The TLR3 signaling complex forms by cooperative receptor dimerization. Proc Natl Acad Sci USA 105, 258-263.
34. Kariko K, Buckstein M, Ni H & Weissman D (2005) Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165-175.
35. Judge AD, Sood V, Shaw JR, Fang D, McClintock K & MacLachlan I (2005) Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 23, 457-462.
36. Prakash TP, Allerson CR, Dande P, Vickers TA, Sioufi N, Jarres R, Baker BF, Swayze EE, Griffey RH & Bhat B (2005) Positional effect of chemical modifications on short interference RNA activity in mammalian cells. J Med Chem 48, 4247-4253.
37. Leuschner PJ, Ameres SL, Kueng S & Martinez J (2006) Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep 7, 314-320.
38. Czauderna F, Fechtner M, Dames S, Aygun H, Klippel A, Pronk GJ, Giese K & Kaufmann J (2003) Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. Nucleic Acids Res 31, 2705-2716.
39. Judge AD, Bola G, Lee AC & MacLachlan I (2006) Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol Ther 13, 494-505.
40. Robbins M, Judge A, Liang L, McClintock K, Yaworski E & MacLachlan I (2007) 2'-O-methyl-modified RNAs act as TLR7 antagonists. Mol Ther 15, 1663-1669.
41. Chiu YL & Rana TM (2003) siRNA function in RNAi: a chemical modification analysis. RNA 9, 1034-1048.
42. Sen G, Flora M, Chattopadhyay G, Klinman DM, Lees A, Mond JJ & Snapper CM (2004) The critical DNA flanking sequences of a CpG oligodeoxynucleotide, but not the 6 base CpG motif, can be replaced with RNA without quantitative or qualitative changes in Toll-like receptor 9-mediated activity. Cell Immunol 232, 64-74.
43. Schlee M, Roth A, Hornung V, Hagmann CA, Wimmenauer V, Barchet W, Coch C, Janke M, Mihailovic A, Wardle G et al. (2009) Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity 31, 25-34.
44. Kim DH, Longo M, Han Y, Lundberg P, Cantin E & Rossi JJ (2004) Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat Biotechnol 22, 321-325.
45. Chiu Y-L, Ali A, Chu C-y, Cao H & Rana TM (2004) Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells. Chemistry & Biology 11, 1165-1175.
46. Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, Elbashir S, Geick A, Hadwiger P, Harborth J et al. (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173-178.
47. Shim MS & Kwon YJ (2010) Efficient and targeted delivery of siRNA in vivo. FEBS J 277, 4814-4827.
48. Sioud M (2005) 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, 1079-1090.
49. Song E, Zhu P, Lee SK, Chowdhury D, Kussman S, Dykxhoorn DM, Feng Y, Palliser D, Weiner DB, Shankar P et al. (2005) Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 23, 709-717.
50. Honda K, Ohba Y, Yanai H, Negishi H, Mizutani T, Takaoka A, Taya C & Taniguchi T (2005) Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434, 1035-1040.
51. Asselin-Paturel C & Trinchieri G (2005) Production of type I interferons: plasmacytoid dendritic cells and beyond. J Exp Med 202, 461-465.
52. Iwasaki A & Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5, 987-995.
53. De Bouteiller O, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, Bates EE & Caux C (2005) Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem 280, 38133-38145.
54. Liu L, Botos I, Wang Y, Leonard JN, Shiloach J, Segal DM & Davies DR (2008) Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 320, 379-381.
55. Pirher N, Ivicak K, Pohar J, Bencina M & Jerala R (2008) A second binding site for double-stranded RNA in TLR3 and consequences for interferon activation. Nat Struct Mol Biol 15, 761-763.
56. Robbins M, Judge A, Ambegia E, Choi C, Yaworski E, Palmer L, McClintock K & MacLachlan I (2008) Misinterpreting the therapeutic effects of small interfering RNA caused by immune stimulation. Hum Gene Ther 19, 991-999.