Effects of chemical modification on the potency, serum stability, and immunostimulatory properties of short shRNAs

RNA

Volumn 16, Issue 1, 2010, Pages 118-130

  Ge, Qing ^a,d   Dallas, Anne ^a   Ilves, Heini ^a   Shorenstein, Joshua ^a   Behlke, Mark A ^b   Johnston, Brian H ^a,c  

^a SomaGenics Inc   (United States)

^b INTEGRATED DNA TECHNOLOGIES   (United States)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d PEKING UNIVERSITY HEALTH SCIENCE CENTER   (China)

Author keywords

Chemical modification; Innate immune response; Serum stability; shRNA; Small hairpin RNA; Stem loop

Indexed keywords

BETA INTERFERON; COMPLEMENTARY RNA; DICER; DIMER; SHORT HAIRPIN RNA; SMALL INTERFERING RNA; TUMOR NECROSIS FACTOR ALPHA; DEOXYRIBONUCLEOTIDE; OLIGONUCLEOTIDE PHOSPHOROTHIOATE;

ARTICLE; CHEMICAL MODIFICATION; CONJUGATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG ACTIVITY; DRUG EFFECT; DRUG POTENCY; DRUG STABILITY; GENE REPRESSION; GENE SILENCING; HUMAN; HUMAN CELL; IMMUNOSTIMULATION; INNATE IMMUNITY; PRIORITY JOURNAL; RNA CLEAVAGE; RNA INTERFERENCE; BIOLOGICAL MODEL; CELL CULTURE; CHEMISTRY; EVALUATION; GENETICS; IMMUNIZATION; IMMUNOLOGY; METABOLISM; METHYLATION; PHYSIOLOGY; POINT MUTATION; RNA STABILITY; SERUM; STRUCTURE ACTIVITY RELATION;

CELLS, CULTURED; DEOXYRIBONUCLEOTIDES; DRUG STABILITY; HUMANS; IMMUNITY, INNATE; IMMUNIZATION; METHYLATION; MODELS, BIOLOGICAL; PHOSPHOROTHIOATE OLIGONUCLEOTIDES; POINT MUTATION; RNA INTERFERENCE; RNA STABILITY; RNA, SMALL INTERFERING; SERUM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 75649128759     PISSN: 13558382     EISSN: 14699001     Source Type: Journal    
DOI: 10.1261/rna.1901810     Document Type: Article

References (63)

1. Allerson CR, Sioufi N, Jarres R, Prakash TP, Naik N, Berdeja A, Wanders L, Griffey RH, Swayze EE, Bhat B. 2005. Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability compared with unmodified small interfering RNA. J Med Chem 48: 901-904. (Pubitemid 40270434)
2. Amarzguioui M, Holen T, Babaie E, Prydz H. 2003. Tolerance for mutations and chemical modifications in a siRNA. Nucleic Acids Res 31: 589-595. (Pubitemid 36175948)
3. Amarzguioui M, Lundberg P, Cantin E, Hagstrom J, Behlke MA, Rossi JJ. 2006. Rational design and in vitro and in vivo delivery of Dicer substrate siRNA. Nat Protoc 1: 508-517.
4. Behlke MA. 2006. Progress towards in vivo use of siRNAs. Mol Ther 13: 644-670.
5. Behlke MA. 2008. Chemical modification of siRNAs for in vivo use. Oligonucleotides 18: 305-319.
6. Bernards R, Brummelkamp TR, Beijersbergen RL. 2006. shRNA libraries and their use in cancer genetics. Nat Methods 3: 701-706. (Pubitemid 44275737)
7. Braasch DA, Jensen S, Liu Y, Kaur K, Arar K, White MA, Corey DR. 2003. RNA interference in mammalian cells by chemically modified RNA. Biochemistry 42: 7967-7975. (Pubitemid 36807714)
8. Bumcrot D, Manoharan M, Koteliansky V, Sah DW. 2006. RNAi therapeutics: A potential new class of pharmaceutical drugs. Nat Chem Biol 2: 711-719. (Pubitemid 44764213)
9. Cekaite L, Furset G, Hovig E, Sioud M. 2007. Gene expression analysis in blood cells in response to unmodified and 29-modified siRNAs reveals TLR-dependent and independent effects. J Mol Biol 365: 90-108. (Pubitemid 44830036)
10. Chang K, Elledge SJ, Hannon GJ. 2006. Lessons from nature: Micro-RNA-based shRNA libraries. Nat Methods 3: 707-714. (Pubitemid 44275738)
11. Chiu YL, Rana TM. 2003. siRNA function in RNAi: A chemical modification analysis. RNA 9: 1034-1048. (Pubitemid 37093614)
12. Choung S, Kim YJ, Kim S, Park HO, Choi YC. 2006. Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochem Biophys Res Commun 342: 919-927. (Pubitemid 43320485)
13. Collingwood MA, Rose SD, Huang L, Hillier C, Amarzguioui M, Wiiger MT, Soifer HS, Rossi JJ, Behlke MA. 2008. Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs. Oligonucleotides 18: 187-200. (Pubitemid 352019751)
14. Czauderna F, Fechtner M, Dames S, Aygun H, Klippel A, Pronk GJ, Giese K, Kaufmann J. 2003. Structural variations and stabilizing modifications of synthetic siRNAs in mammalian cells. Nucleic Acids Res 31: 2705-2716. (Pubitemid 37442115)
15. Debart F, Abes S, Deglane G, Moulton HM, Clair P, Gait MJ, Vasseur JJ, Lebleu B. 2007. Chemical modifications to improve the cellular uptake of oligonucleotides. Curr Top Med Chem 7: 727-737. (Pubitemid 46681854)
16. Dorsett Y, Tuschl T. 2004. siRNAs: Applications in functional genomics and potential as therapeutics. Nat Rev Drug Discov 3: 318-329. (Pubitemid 38499759)
17. Eder PS, DeVine RJ, Dagle JM, Walder JA. 1991. Substrate specificity and kinetics of degradation of antisense oligonucleotides by a 39 exonuclease in plasma. Antisense Res Dev 1: 141-151.
18. 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. (Pubitemid 32494397)
19. Fewell GD, Schmitt K. 2006. Vector-based RNAi approaches for stable, inducible and genome-wide screens. Drug Discov Today 11: 975-982. (Pubitemid 44572884)
20. 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 sequencespecific TLR8-dependent immune responses. J Immunol 180: 3729-3738.
21. Ge Q, Ilves H, Dallas A, Kumar P, Shorenstein J, Kazakov SA, Johnston BH. 2010. Minimal-length short hairpin RNAs: The relationship of structure and RNAi activity. RNA (this issue). doi: 10.1261/rna.1894510.
22. Gonzalez-Gonzalez E, Ra H, Hickerson RP, Wang Q, Piyawattanametha W, Mandella MJ, Kino GS, Leake D, Avilion AA, Solgaard O, et al. 2009. siRNA silencing of keratinocyte-specific GFP expression in a transgenic mouse skin model. Gene Ther 16: 963-972.
23. Harborth J, Elbashir SM, Vandenburgh K, Manninga H, Scaringe SA, Weber K, Tuschl T. 2003. Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Antisense Nucleic Acid Drug Dev 13: 83-105.
24. Harper SQ, Staber PD, He X, Eliason SL, Martins IH, Mao Q, Yang L, Kotin RM, Paulson HL, Davidson BL. 2005. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc Natl Acad Sci 102: 5820-5825. (Pubitemid 40559643)
25. Hayashi F, Means TK, Luster AD. 2003. Toll-like receptors stimulate human neutrophil function. Blood 102: 2660-2669. (Pubitemid 37193610)
26. 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-a by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11: 263-270. (Pubitemid 40460553)
27. Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann KK, Schlee M, et al. 2006. 59-Triphosphate RNA is the ligand for RIG-I. Science 314: 994-997.
28. Jackson AL, Burchard J, Leake D, Reynolds A, Schelter J, Guo J, Johnson JM, Lim L, Karpilow J, Nichols K, et al. 2006. Positionspecific chemical modification of siRNAs reduces 'off-target' transcript silencing. RNA 12: 1197-1205.
29. Jinek M, Doudna JA. 2009. A three-dimensional view of the molecular machinery of RNA interference. Nature 457: 405-412.
30. Judge A, MacLachlan I. 2008. Overcoming the innate immune response to small interfering RNA. Hum Gene Ther 19: 111-124. (Pubitemid 351271512)
31. 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. (Pubitemid 41724921)
32. 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. (Pubitemid 43257617)
33. 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. (Pubitemid 38669088)
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. (Pubitemid 41169286)
35. 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. (Pubitemid 38295765)
36. Kurreck J. 2003. Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem 270: 1628-1644. (Pubitemid 36532522)
37. Levin AA. 1999. A review of the issues in the pharmacokinetics and toxicology of phosphorothioate antisense oligonucleotides. Biochim Biophys Acta 1489: 69-84.
38. Li L, Lin X, Khvorova A, Fesik SW, Shen Y. 2007. Defining the optimal parameters for hairpin-based knockdown constructs. RNA 13: 1765-1774. (Pubitemid 47481684)
39. 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.
40. 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.
41. McManus MT, Petersen CP, Haines BB, Chen J, Sharp PA. 2002. Gene silencing using micro-RNA designed hairpins. RNA 8: 842-850. (Pubitemid 34620459)
42. 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.
43. Nawrot B, Sipa K. 2006. Chemical and structural diversity of siRNA molecules. Curr Top Med Chem 6: 913-925. (Pubitemid 43796971)
44. Nishina K, Unno T, Uno Y, Kubodera T, Kanouchi T, Mizusawa H, Yokota T. 2008. Efficient in vivo delivery of siRNA to the liver by conjugation of a-tocopherol. Mol Ther 16: 734-740. (Pubitemid 351426175)
45. Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya SS, Kirschnek S, Gaffal E, Landsberg J, Hellmuth J, et al. 2008. 59-Triphosphate-siRNA: Turning gene silencing and Rig-I activation against melanoma. Nat Med 14: 1256-1263.
46. Ranjith-Kumar CT, Murali A, Dong W, Srisathiyanarayanan D, Vaughan R, Ortiz-Alacantara J, Bhardwaj K, Li X, Li P, Kao CC. 2009. Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor. J Biol Chem 284: 1155-1165.
47. Reynolds A, Anderson EM, Vermeulen A, Fedorov Y, Robinson K, Leake D, Karpilow J, Marshall WS, Khvorova A. 2006. Induction of the interferon response by siRNA is cell type- and duplex length-dependent. RNA 12: 988-993. (Pubitemid 43788117)
48. Robbins M, Judge A, Liang L, McClintock K, Yaworski E, MacLachlan I. 2007. 29-O-methyl-modified RNAs act as TLR7 antagonists. Mol Ther 15: 1663-1669. (Pubitemid 47289010)
49. 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.
50. Robbins M, Judge A, MacLachlan I. 2009. siRNA and innate immunity. Oligonucleotides 19: 89-102.
51. Schlee M, Hornung V, Hartmann G. 2006. siRNA and isRNA: Two edges of one sword. Mol Ther 14: 463-470. (Pubitemid 44296098)
52. Siolas D, Lerner C, Burchard J, Ge W, Linsley PS, Paddison PJ, Hannon GJ, Cleary MA. 2005. Synthetic shRNAs as potent RNAi triggers. Nat Biotechnol 23: 227-231. (Pubitemid 40255334)
53. 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. (Pubitemid 40602367)
54. 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.
55. Takeuchi O, Akira S. 2009. Innate immunity to virus infection. Immunol Rev 227: 75-86.
56. Terhorst D, Kalali BN, Weidinger S, Illig T, Novak N, Ring J, Ollert M, Mempel M. 2007. Monocyte-derived dendritic cells from highly atopic individuals are not impaired in their proinflammatory response to toll-like receptor ligands. Clin Exp Allergy 37: 381-390. (Pubitemid 46393237)
57. Ui-Tei K, Naito Y, Zenno S, Nishi K, Yamato K, Takahashi F, Juni A, Saigo K. 2008. Functional dissection of siRNA sequence by systematic DNA substitution: Modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. Nucleic Acids Res 36: 2136-2151. (Pubitemid 351566989)
58. Vlassov AV, Korba B, Farrar K, Mukerjee S, Seyhan AA, Ilves H, Kaspar RL, Leake D, Kazakov SA, Johnston BH. 2007. shRNAs targeting hepatitis C: Effects of sequence and structural features, and comparision with siRNA. Oligonucleotides 17: 223-236. (Pubitemid 47124419)
59. Wang Q, Contag CH, Ilves H, Johnston BH, Kaspar RL. 2005. Small hairpin RNAs efficiently inhibit hepatitis C IRES-mediated gene expression in human tissue culture cells and a mouse model. Mol Ther 12: 562-568. (Pubitemid 41150143)
60. Watts JK, Deleavey GF, Damha MJ. 2008. Chemically modified siRNA: Tools and applications. Drug Discov Today 13: 842-855.
61. Xia H, Mao Q, Paulson HL, Davidson BL. 2002. siRNA-mediated gene silencing in vitro and in vivo. Nat Biotechnol 20: 1006-1010.
62. Xia H, Mao Q, Eliason SL, Harper SQ, Martins IH, Orr HT, Paulson HL, Yang L, Kotin RM, Davidson BL. 2004. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med 10: 816-820. (Pubitemid 39070854)
63. Zhang HY, Du Q, Wahlestedt C, Liang Z. 2006. RNA Interference with chemically modified siRNA. Curr Top Med Chem 6: 893-900. (Pubitemid 43796969)