Running interference: Prospects and obstacles to using small interfering RNAs as small molecule drugs

Annual Review of Biomedical Engineering

Volumn 8, Issue , 2006, Pages 377-402

  Dykxhoorn, Derek M ^a   Lieberman, Judy ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Drug development; In vivo delivery; RNA interference; Therapy

Indexed keywords

BIODIVERSITY; CELLS; CYTOLOGY; DISEASE CONTROL; DRUG PRODUCTS; GENETIC ENGINEERING; VIRUSES;

DRUG DEVELOPMENT; IN VIVO DELIVERY; RNA INTERFERENCE (RNAI); THERAPY;

RNA;

ALBUMIN; ALPHA INTERFERON; ANTISENSE OLIGONUCLEOTIDE; CELL ENZYME; CELL PROTEIN; CHEMOKINE RECEPTOR CCR5; CYTOSINE; DOUBLE STRANDED RNA; ENDONUCLEASE; EXPORTIN 5; GUANINE; HELICASE; LIPOPROTEIN RECEPTOR; MAGNESIUM ION; MESSENGER RNA; MICRORNA; NUCLEASE; NUCLEOTIDE DERIVATIVE; RIBONUCLEASE III; RIBOZYME; RNA BINDING PROTEIN; SMALL INTERFERING RNA; TOLL LIKE RECEPTOR; TRANSACTIVATOR PROTEIN; UNINDEXED DRUG; URIDINE; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2;

CELL DEATH; CELL DIFFERENTIATION; CELL MATURATION; DRUG ACTIVITY; DRUG DELIVERY SYSTEM; DRUG MECHANISM; DRUG SPECIFICITY; DRUG TARGETING; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE SILENCING; GENOME; HUMAN; NONHUMAN; REVIEW; RNA INTERFERENCE; RNA PROCESSING; RNA SEQUENCE; TRANSPOSON;

ANIMALS; DRUG DELIVERY SYSTEMS; GENE SILENCING; GENE TARGETING; GENE THERAPY; HUMANS; MODELS, GENETIC; RNA, SMALL INTERFERING;

MAMMALIA;

EID: 33748201603     PISSN: 15239829     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.bioeng.8.061505.095848     Document Type: Review

References (130)

1. Dykxhoorn DM, Novina CD, Sharp PA. 2003. Killing the messenger: short RNAs that silence gene expression. Nat. Rev. Mol. Cell Biol. 4:457-67
2. Samakoglu S, Lisowski L, Budak-Alpdogan T, Usachenko Y, Acuto S, et al. 2006. A genetic strategy to treat sickle cell anemia by coregulating globin transgene expression and RNA interference. Nat. Biotechnol. 24:89-94
3. Morris KV, Rossi JJ. 2006. Lentiviral-mediated delivery of siRNAs for antiviral therapy. Gene Ther. 13:553-58
4. Noguchi P. 2003. Risks and benefits of gene therapy. N. Engl. J. Med. 348:193-94
5. Campochiaro PA. 2006. Potential applications for RNAi to probe pathogenesis and develop new treatments for ocular disorders. Gene Ther. 13:559-62
6. Dykxhoorn DM, Palliser D, Lieberman J. 2006. The silent treatment: siRNAs as small molecule drugs. Gene Ther. 13:541-52
7. Dykxhoorn DM, Lieberman J. 2005. The silent revolution: RNA interference as basic biology, research tool, and therapeutic. Annu. Rev. Med. 56:401-23
8. Lippman Z, Martienssen R. 2004. The role of RNA interference in heterochromatic silencing. Nature 431:364-70
9. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabdhis elegans. Nature 391:806-11
10. Tuschl T, Zamore PD, Lehmann R, Bartel DP, Sharp PA. 1999. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev. 13:3191-97
11. Zamore PD, Tuschl T, Sharp PA, Bartel DP. 2000. RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101:25-33
12. Hammond SM, Bernstein E, Beach D, Hannon GJ. 2000. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404:293-96
13. Yang D, Lu H, Erickson JW. 2000. Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Curr. Biol. 10:1191-200
14. Parrish S, Fleenor J, Xu S, Mello C, Fire A. 2000. Functional anatomy of a dsRNA trigger: differential requirement for the two trigger strands in RNA interference. Mol. Cell 6:1077-87
15. Elbashir SM, Lendeckel W, Tuschl T. 2001. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15:188-200
16. Bernstein E, Gaudy AA, Hammond SM, Hannon GJ. 2001. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363-66
17. 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 411:494-98
18. Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD. 2003. Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199-208
19. Khvorova A, Reynolds A, Jayasena SD. 2003. Functional siRNAs and miRNAs exhibit strand bias. Cell 115:209-16
20. Liu Q, Rand TA, Kalidas S, Du F, Kim HE, et al. 2003. R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science 301:1921-25
21. Tomari Y, Matranga C, Haley B, Martinez N, Zamore PD. 2004. A protein sensor for siRNA asymmetry. Science 306:1377-80
22. Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. 2001. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293:1146-50
23. Okamura K, Ishizuka A, Siomi H, Siomi MC. 2004. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev. 18:1655-66
24. Rand TA, Ginalski K, Grishin NV, Wang X. 2004. Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity. Proc. Natl. Acad. Sci. USA 101:14385-89
25. Tomari Y, Du T, Haley B, Schwarz DS, Bennett R, et al. 2004. RISC assembly defects in the Drosophila RNAi mutant armitage. Cell 116:831-41
26. Rand TA, Petersen S, Du F, Wang X. 2005. Argonaute2 cleaves the antiguide strand of siRNA during RISC activation. Cell 123:621-29
27. Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD. 2005. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123:607-20
28. Ma JB, Yuan YR, Meister G, Pei Y, Tuschl T, Patel DJ. 2005. Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 434:666-70
29. Lewis BP, Burge CB, Bartel DP. 2005. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15-20
30. Lingel A, Sattler M. 2005. Novel modes of protein-RNA recognition in the RNAi pathway. Curr. Opin. Struct. Biol. 15:107-15
31. Schwarz DS, Tomari Y, Zamore PD. 2004. The RNA-induced silencing complex is a Mg2-dependent endonuclease. Curr. Biol. 14:787-91
32. Martinez J, Tuschl T. 2004. RISC is a 5′ phosphomonoester-producing RNA endonuclease. Genes Dev. 18:975-80
33. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, et al. 2004. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437-41
34. Hutvagner G, Zamore PD. 2002. A microRNA in a multiple-turnover RNAi enzyme complex. Science 297:2056-60
35. Du T, Zamore PD. 2005. microPrimer: the biogenesis and function of microRNA. Development 132:4645-52
36. Doench JG, Petersen CP, Sharp PA. 2003. siRNAs can function as miRNAs. Genes Dev. 17:438-42
37. Kim VN. 2005. MicroRNA biogenesis: coordinated cropping and dicing. Nat. Rev. Mol. Cell Biol. 6:376-85
38. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. 2004. Processing of primary microRNAs by the Microprocessor complex. Nature 432:231-35
39. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, et al. 2004. The Microprocessor complex mediates the genesis of microRNAs. Nature 432:235-40
40. Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. 2004. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 18:3016-27
41. Landthaler M, Yalcin A, Tuschl T. 2004. The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Curr. Biol. 14:2162-67
42. Lee Y, Ahn C, Han J, Choi H, Kim J, et al. 2003. The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415-19
43. Yi R, Qin Y, Macara IG, Cullen BR. 2003. Exportin-5 mediates the nuclear export of premicroRNAs and short hairpin RNAs. Genes Dev. 17:3011-16
44. Yi R, Doehle BP, Qin Y, Macara IG, Cullen BR. 2005. Overexpression of exportin 5 enhances RNA interference mediated by short hairpin RNAs and microRNAs. RNA 11:220-26
45. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. 2004. Nuclear export of microRNA precursors. Science 303:95-98
46. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, et al. 2001. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106:23-34
47. Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. 2001. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293:834-38
48. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, et al. 2005. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436:740-44
49. Forstemann K, Tomari Y, Du T, Vagin W, Denli AM, et al. 2005. Normal micro RNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol. 3:e236
50. Jiang F, Ye X, Liu X, Fincher L, McKearin D, Liu Q. 2005. Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes Dev. 19:1674-79
51. Saito K, Ishizuka A, Siomi H, Siomi MC. 2005. Processing of premicroRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol. 3:e235
52. Rhoades MW, Reinhart BJ, Lim LP, Burge CB, Bartel B, Bartel DP. 2002. Prediction of plant microRNA targets. Cell 110:513-20
53. Llave C, Xie Z, Kasschau KD, Carrington JC. 2002. Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science 297:2053-56
54. Tang G, Reinhart BJ, Bartel DP, Zamore PD. 2003. A biochemical framework for RNA silencing in plants. Genes Dev. 17:49-63
55. Bartel DP. 2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281-97
56. Jakymiw A, Lian S, Eystathioy T, Li S, Satoh M, et al. 2005. Disruption of GW bodies impairs mammalian RNA interference. Nat. Cell Biol. 7:1167-74
57. Liu J, Rivas FV, Wohlschlegel J, Yates JR, Parker R, Hannon GJ. 2005. A role for the P-body component GW182 in microRNA function. Nat. Cell Biol. 7:1161-66
58. Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. 2005. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat. Cell Biol. 7:719-21
59. Meister G, Landthaler M, Peters L, Chen PY, Urlaub H, et al. 2005. Identification of novel Argonaute-associated proteins. Curr. Biol. 15:2149-55
60. Rehwinkel J, Behm-Ansmant I, Gatfield D, Izaurralde E. 2005. A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA 11:1640-47
61. Sen GL, Blau HM. 2005. Argonaute 2RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat. Cell Biol. 7:633-36
62. Scherer LJ, Rossi JJ. 2003. Approaches for the sequence-specific knockdown of mRNA. Nat. Biotechnol. 21:1457-65
63. Dorsett Y, Tuschl T. 2004. siRNAs: applications in functional genomics and potential as therapeutics. Nat. Rev. Drug Discov. 3:318-29
64. Crooke ST. 1999. Molecular mechanisms of action of antisense drugs. Biochim. Biophys. Acta 1489:31-44
65. Dias N, Stein CA. 2002. Antisense oligonucleotides: basic concepts and mechanisms. Mol. Cancer Ther. 1:347-55
66. Grunweller A, Wyszko E, Bieber B, Jahnel R, Erdmann VA, Kurreck J. 2003. Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2′-O-methyl RNA, phosphorothioates and small interfering RNA. Nucleic Acids Res. 31:3185-93
67. Vickers TA, Koo S, Bennett CF, Crooke ST, Dean NM, Baker BF. 2003. Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. A comparative analysis. J. Biol. Chem. 278:7108-18
68. Giles RV, Tidd DM. 1992. Increased specificity for antisense oligodeoxynucleotide targeting of RNA cleavage by RNase H using chimeric methylphosphonodiesterphosphodiester structures. Nucleic Acids Res. 20:763-70
69. Bertrand JR, Pottier M, Vekris A, Opolon P, Maksimenko A, Malvy C. 2002. Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo. Biochem. Biophys. Res. Commun. 296:1000-4
70. Robinson R. 2004. RNAi therapeutics: how likely, how soon? PLoS Biol. 2:e28
71. Bai J, Banda N, Lee NS, Rossi J, Akkina R. 2002. RNA-based anti-HIV-1 gene therapeutic constructs in SCID-hu mouse model. Mol. Ther. 6:770-82
72. Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, Khvorova A. 2004. Rational siRNA design for RNA interference. Nat. Biotechnol. 22:326-30
73. Boese Q, Leake D, Reynolds A, Read S, Scaringe SA, et al. 2005. Mechanistic insights aid computational short interfering RNA design. Methods Enzymol. 392:73-96
74. 73a. Dykxhoorn DM, Schlehuber LD, London IM, Lieberman J. 2006. Determinants of specific RNA interference-mediated silencing of human β-globin alleles differing by a single nucleotide polymorphism. Proc. Natl. Acad. USA. 103:5953-58
75. Kim DH, Behlke MA, Rose SD, Chang MS, Choi S, Rossi JJ. 2005. Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nat. Biotechnol. 23:222-26
76. Morrissey DV, Blanchard K, Shaw L, Jensen K, Lockridge JA, et al. 2005. Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41:1349-56
77. Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, et al. 2005. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat. Biotechnol. 23:1002-7
78. Czauderna F, Fechtner M, Dames S, Aygun H, Klippel A, et al. 2003. Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. Nucleic Acids Res. 31:2705-16
79. Capodici J, Kariko K, Weissman D. 2002. Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J. Immunol. 169:5196-201
80. Chiu YL, Rana TM. 2003. siRNA function in RNAi: a chemical modification analysis. RNA 9:1034-48
81. Layzer JM, McCaffrey AP, Tanner AK, Huang Z, Kay MA, Sullenger BA. 2004. In vivo activity of nuclease-resistant siRNAs. RNA 10:766-71
82. Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T. 2001. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J. 20:6877-88
83. Braasch DA, Jensen S, Liu Y, Kaur K, Arar K, et al. 2003. RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42:7967-75
84. Harborth J, Elbashir SM, Vandenburgh K, Manninga H, Scaringe SA, et al. 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
85. Song E, Lee SK, Dykxhoorn DM, Novina C, Zhang D, et al. 2003. Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages. J. Virol. 77:7174-81
86. Song E, Lee SK, Wang J, Ince N, Ouyang N, et al. 2003. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat. Med. 9:347-51
87. Zhang X, Shan P, Jiang D, Noble PW, Abraham NG, et al. 2004. Small interfering RNA targeting heme oxygenase-1 enhances ischemia-reperfusion-induced lung apoptosis. J. Biol. Chem. 279:10677-84
88. Li BJ, Tang Q, Cheng D, Qin C, Xie FY, et al. 2005. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque. Nat. Med. 11:944-51
89. Palliser D, Chowdhury D, Wang QY, Lee SJ, Bronson RT, et al. 2006. An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature 439:89-94
90. Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, et al. 2004. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432:173-78
91. Urban-Klein B, Werth S, Abuharbeid S, Czubayko F, Aigner A. 2005. RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther. 12:461-66
92. Boutros M, Kiger AA, Armknecht S, Kerr K, Hild M, et al. 2004. Genome-wide RNAi analysis of growth and viability in Drosophila cells. Science 303:832-35
93. Tabara H, Grishok A, Mello CC. 1998. RNAi in C. elegans: soaking in the genome sequence. Science 282:430-31
94. Stewart SA, Dykxhoorn DM, Palliser D, Mizuno H, Yu EY, et al. 2003. Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA 9:493-501
95. Bitko V, Musiyenko A, Shulyayeva O, Barik S. 2005. Inhibition of respiratory viruses by nasally administered siRNA. Nat. Med. 11:50-55
96. Ge Q, Filip L, Bai A, Nguyen T, Eisen HN, Chen J. 2004. Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc. Natl. Acad. Sci. USA 101:8676-81
97. Tompkins SM, Lo CY, Tumpey TM, Epstein SL. 2004. Protection against lethal influenza virus challenge by RNA interference in vivo. Proc. Natl. Acad. Sci. USA 101:8682-86
98. Reich SJ, Fosnot J, Kuroki A, Tang W, Yang X, et al. 2003. Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Mol. Vis. 9:210-16
99. Kim B, Tang Q, Biswas PS, Xu J, Schiffelers RM, et al. 2004. Inhibition of ocular angiogenesis by siRNA targeting vascular endothelial growth factor pathway genes: therapeutic strategy for herpetic stromal keratitis. Am. J. Pathol. 165:2177-85
100. Shen J, Samul R, Silva RL, Akiyama H, Liu H, et al. 2006. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Ther. 13:225-34
101. Simeoni F, Morris MC, Heitz F, Divita G. 2003. Insight into the mechanism of the peptide-based gene delivery system MPG: implications for delivery of siRNA into mammalian cells. Nucleic Acids Res. 31:2717-24
102. Simeoni F, Morris MC, Heitz F, Divita G. 2005. Peptide-based strategy for siRNA delivery into mammalian cells. Methods Mol. Biol. 309:251-60
103. Rittner K, Benavente A, Bompard-Sorlet A, Heitz F, Divita G, et al. 2002. New basic membrane-destabilizing peptides for plasmid-based gene delivery in vitro and in vivo. Mol. Ther. 5:104-14
104. Song E, Zhu P, Lee SK, Chowdhury D, Kussman S, et al. 2005. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat. Biotechnol. 23:709-17
105. Kang H, Delong R, Fisher MH, Juliano RL. 2005. Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides. Pharm. Res. 22:2099-306
106. Bridge AJ, Pebernard S, Ducraux A, Nicoulaz AL, Iggo R. 2003. Induction of an interferon response by RNAi vectors in mammalian cells. Nat. Genet. 34:263-64
107. Persengiev SP, Zhu X, Green MR. 2004. Nonspecific, concentration- dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 10:12-18
108. Sledz CA, Holko M, de Veer MJ, Silverman RH, Williams BR. 2003. Activation of the interferon system by short-interfering RNAs. Nat. Cell Biol. 5:834-39
109. 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. 23:457-62
110. Heidel JD, Hu S, Liu XF, Triche TJ, Davis ME. 2004. Lack of interferon response in animals to naked siRNAs. Nat. Biotechnol. 22:1579-82
111. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, et al. 2005. Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11:263-70
112. Marques JT, Williams BR. 2005. Activation of the mammalian immune system by siRNAs. Nat. Biotechnol. 23:1399-405
113. 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. 348:1079-90
114. Fedorov Y, King A, Anderson E, Karpilow J, Ilsley D, et al. 2005. Different delivery methods-different expression profiles. Nat. Methods 2:241
115. 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
116. Saxena S, Jonsson ZO, Dutta A. 2003. Small RNAs with imperfect match to endogenous mRNA repress translation. Implications for off-target activity of small inhibitory RNA in mammalian cells. J. Biol. Chem. 278:44312-19
117. Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, et al. 2003. Expression profiling reveals off-target gene regulation by RNAi. Nat. Biotechnol. 21:635-37
118. Jackson AL, Linsley PS. 2004. Noise amid the silence: off-target effects of siRNAs? Trends Genet. 20:521-24
119. Schubert S, Grunweller A, Erdmann VA, Kurreck J. 2005. Local RNA target structure influences siRNA efficacy: systematic analysis of intentionally designed binding regions. J. Mol. Biol. 348:883-93
120. Overhoff M, Alken M, Far RK, Lemaitre M, Lebleu B, et al. 2005. Local RNA target structure influences siRNA efficacy: a systematic global analysis. J. Mol. Biol. 348:871-81
121. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. 2004. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol. Cell 15:185-97
122. Minalcuchi Y, Takeshita F, Kosaka N, Sasaki H, Yamamoto Y, et al. 2004. Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo. Nucleic Acids Res. 32:e109
123. Leng Q, Mixson AJ. 2005. Small interfering RNA targeting Raf-1 inhibits tumor growth in vitro and in vivo. Cancer Gene Ther. 12:682-90
124. Dorn G, Patel S, Wotherspoon G, Hemmings-Mieszczak M, Barclay J, et al. 2004. siRNA relieves chronic neuropathic pain. Nucleic Acids Res. 32:e49
125. Hagstrom JE, Hegge J, Zhang G, Noble M, Budker V, et al. 2004. A facile non-viral method for delivering genes and siRNAs to skeletal muscle of mammalian limbs. Mol. Ther. 10:386-98
126. McCaffrey AP, Meuse L, Pham TT, Conklin DS, Hannon GJ, Kay MA. 2002. RNA interference in adult mice. Nature 418:38-39
127. McCaffrey AP, Nakai H, Pandey K, Huang Z, Salazar FH, et al. 2003. Inhibition of hepatitis B virus in mice by RNA interference. Nat. Biotechnol. 21:639-44
128. Giladi H, Ketzinel-Gilad M, Rivkin L, Felig Y, Nussbaum O, Galun E. 2003. Small interfering RNA inhibits hepatitis B virus replication in mice. Mol. Ther. 8:769-76
129. Wesche-Soldato DE, Chung CS, Lomas-Neira J, Doughty LA, Gregory SH, Ayala A. 2005. In vivo delivery of caspase-8 or Fas siRNA improves the survival of septic mice. Blood 106:2295-301
130. Zender L, Hutker S, Liedtke C, Tillmann HL, Zender S, et al. 2003. Caspase 8 small interfering RNA prevents acute liver failure in mice. Proc. Natl. Acad. Sci. USA 100:7797-802