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Targeting Viral Heart Disease by RNA Interference

  • S. Merl
  • R. WesselyEmail author
Chapter
  • 283 Downloads

Abstract

Viral heart disease (VHD) is an important clinical disease entity both in pediatric as well as adult cardiology. Coxsackieviruses (CVBs) are considered an important cause for VHD in both populations. VHD may lead to dilated cardiomyopathy and heart failure which can ultimately require heart transplantation. However, no specific treatment modality is so far available. We and others have shown that coxsackieviral replication and cytotoxicity can be successfully targeted by RNA interference, thus leading to increased cell viability and even prolongation of survival in vivo. However, considerable limitations have to be solved before this novel therapeutic approach may enter the clinical trials arena.

Keywords

Human Immunodeficiency Virus Type Respiratory Syncytial Virus Respiratory Syncytial Virus Infection Lock Nucleic Acid siRNA Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Abrahante J, Daul A, Li M et al (2003) The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Dev Cell 4:625–637PubMedCrossRefGoogle Scholar
  2. Ahn J, Jun E, Lee H et al (2005) A small Interfering RNA targeting coxsackievirus B3 protects permissive HeLa cells from viral challenge. J Virol 79:8620–8624PubMedCrossRefGoogle Scholar
  3. Alisky J, Davidson B (2004) Towards therapy using RNA interference. Am J Pharmacogenomics 4:45–51PubMedCrossRefGoogle Scholar
  4. Allerson C, Sioufi N, Jarres R et al (2005) Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA. J Med Chem 48:901–904PubMedCrossRefGoogle Scholar
  5. Arts G, Langemeijer E, Tissingh R et al (2003) Adenoviral vectors expressing siRNAs for discovery and validation of gene function. Genom Res 13:2325–2332CrossRefGoogle Scholar
  6. Badorff C, Lee G, Lamphear B et al (1999) Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an aquired cardiomyopathy. Nat Med 5:320–326PubMedCrossRefGoogle Scholar
  7. Barik S (2005) Silence of the transcripts: RNA interference in medicine. J Mol Med 83:764–773PubMedCrossRefGoogle Scholar
  8. Bauer S, Gottesman G, Sirota L et al (2002) Severe coxsackie virus B infection in preterm newborns treated with pleconaril. Eur J Pediatr 161:491–493PubMedCrossRefGoogle Scholar
  9. Bergelson J, Cunningham J, Droguett G et al (1997) Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science 275:1320–1323PubMedCrossRefGoogle Scholar
  10. Bernstein E, Caudy A, Hammond S et al (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366PubMedCrossRefGoogle Scholar
  11. Bhuyan P, Kariko K, Capodici J et al (2004) Short interfering RNA-mediated inhibition of herpes simplex virus type 1 gene expression and function during infection of human keratinocytes. J Virol 78:10276–10281PubMedCrossRefGoogle Scholar
  12. Billy E, Brondani V, Zhang H et al (2001) Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines. Proc Natl Acad Sci USA 98:14428–14433PubMedCrossRefGoogle Scholar
  13. Bitko V, Barik S (2001) Phenotypic silencing of cytoplasmic genes using sequence-specific double-stranded short interfering RNA and its application in the reverse genetics of wild type negative-strand RNA viruses. BMC Microbiol 1:34PubMedCrossRefGoogle Scholar
  14. Bitko V, Musiyenko A, Shulyayeva O et al. (2005) Inhibition of repiratory viruses by nasally administered siRNA. Nat Med 11:50–55PubMedCrossRefGoogle Scholar
  15. Boden D, Pusch O, Lee F et al (2003) Human immunodeficiency virus type 1 escape from RNA interference. J Virol 77:11531–11535PubMedCrossRefGoogle Scholar
  16. Bohula E, Salisbury A, Sohail M et al (2003) The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R transcript. J Biol Chem 278:15991–15997PubMedCrossRefGoogle Scholar
  17. Braasch D, Jensen S, Liu Y et al (2003) RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42:7967–7975PubMedCrossRefGoogle Scholar
  18. Brennecke J, Hipfner D, Stark A et al (2003) Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113:25–36PubMedCrossRefGoogle Scholar
  19. Brown K, Chu C, Rana T (2005) Target accessibility dictates the potency of human RISC. Nat Struct Mol Biol 12:469–470PubMedCrossRefGoogle Scholar
  20. Brummelkamp T, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550–553PubMedCrossRefGoogle Scholar
  21. Chen Z, Indjeian V, McManus M et al (2002) CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells. Dev Cell 3:339–350PubMedCrossRefGoogle Scholar
  22. Chi J, Chang H, Wang N et al (2003) Genomewide view of gene silencing by small interfering RNAs. Proc Natl Acad Sci USA 100:6343–6346PubMedCrossRefGoogle Scholar
  23. Coburn G, Cullen B (2002) Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference. J Virol 76:9225–9231PubMedCrossRefGoogle Scholar
  24. Das AT, Brummelkamp T, Westerhout E et al (2004) Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. J Virol 78:2601–2605PubMedCrossRefGoogle Scholar
  25. deFougerolles A, Manoharan M, Meyers R et al (2005) RNA interference in vivo: towards synthetic small inhibitory RNA-based therapeutics. Methods Enzymol 392:278–296PubMedCrossRefGoogle Scholar
  26. Ding Y, Chan C, Lawrence C (2004) Sfold web server for statistical folding and rational design of nucleic acids. Nucleic Acids Res 32:135–141CrossRefGoogle Scholar
  27. Dorsett Y, Tuschl T (2004) siRNAs: application in functional genomics and potential as therapeutics. Nat Rev Drug Discov 3:318–329PubMedCrossRefGoogle Scholar
  28. Downward J (2004) RNA interference. BMJ 328:1245–1248PubMedCrossRefGoogle Scholar
  29. Dykxhoorn D, Novina C, Sharp P (2003) Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol 4:457–467PubMedCrossRefGoogle Scholar
  30. Elbashir S, Harborth J, Lendeckel W et al (2001a) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498PubMedCrossRefGoogle Scholar
  31. Elbashir S, Lendeckel W, Tuschl T (2001b) RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15:188–200PubMedCrossRefGoogle Scholar
  32. Elmen J, Thonberg H, Ljungberg K et al (2005) Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res 33:439–447PubMedCrossRefGoogle Scholar
  33. Fechner H, Pinkert S, Wang X et al (2007) Coxsackievirus B3 and adenovirus infections of cardiac cells are efficiently inhibited by vector-mediated RNA interference targeting their common receptor. Gene Ther 14:960–971PubMedCrossRefGoogle Scholar
  34. Feldman A, McNamara D (2000) Myocarditis. N Engl J Med 343:1388–1398PubMedCrossRefGoogle Scholar
  35. Feuer R, Mena I, Pagarigan R et al (2003) Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am J Pathol 163:1379–1393PubMedGoogle Scholar
  36. Fire A, Xu S, Montgomery M et al (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811PubMedCrossRefGoogle Scholar
  37. Friedrich I, Shir A, Klein S et al (2004) RNA molecules as anti-cancer agents. Semin Cancer Biol 14(4):223–230PubMedCrossRefGoogle Scholar
  38. Gartel A, Kandel E (2006) RNA interference in cancer. Biomol Eng 23(1):17–34PubMedCrossRefGoogle Scholar
  39. Ge Q, McManus M, Nguyen T et al (2003) RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription. Proc Natl Acad Sci USA 100:2718–2723PubMedCrossRefGoogle Scholar
  40. Ge Q, Filip L, Bai A et al (2004) Inhibition of influenza virus production in virus infected mice by RNA interference. Proc Natl Acad Sci USA 101:8676–8681PubMedCrossRefGoogle Scholar
  41. Giladi H, Ketzinel-Gilad M, Rivkin L et al (2003) Small interfering RNA inhibits hepatitis B virus replication in mice. Mol Ther 8:769–776PubMedCrossRefGoogle Scholar
  42. Gitlin L, Karelsky S, Andino R (2002) Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 418:430–434PubMedCrossRefGoogle Scholar
  43. Gitlin L, Stone J, Andino R (2005) Poliovirus Escape from RNA Interference: short interfering RNA-target recognition and implications for therapeutic approaches. J Virol 79:1027–1035PubMedCrossRefGoogle Scholar
  44. Grishok A, Mello C (2002) RNAi (Nematodes: Caenorhabditis elegans). Adv Genet 46:339–360PubMedCrossRefGoogle Scholar
  45. Hamasaki K, Nakao K, Matsumoto K et al (2003) Short interfering RNA-directed inhibition of hepatitis B virus replication. FEBS Lett 543:51–54PubMedCrossRefGoogle Scholar
  46. Hammond S, Bernstein E, Beach D et al (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404:293–296PubMedCrossRefGoogle Scholar
  47. Hammond S, Caudy A, Hannon G (2001) Post-transcriptional gene silencing by double-stranded RNA. Nat Rev Genet 2:110–119PubMedCrossRefGoogle Scholar
  48. Harborth J, Elbashir S, Vandenburgh K 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 13:83–105PubMedCrossRefGoogle Scholar
  49. Heale B, Soifer H, Bowers C et al (2005) siRNA target site secondary structure predictions using local stable substructures. Nucleic Acids Res 33:e30PubMedCrossRefGoogle Scholar
  50. Holen T, Amarzguioui M, Wiiger M et al (2002) Positional effects of short interfering RNAs targeting the human coagulation trigger tissue factor. Nucleic Acids Res 30(8):1757–1766PubMedCrossRefGoogle Scholar
  51. Hu W, Myers C, Kilzer J et al (2002) Inhibition of retroviral pathogenesis by RNA interference. Curr Biol 12:1301–1311PubMedCrossRefGoogle Scholar
  52. Jacque J, Triques K, Stevenson M (2002) Modulation of HIV-1 replication by RNA interference. Nature 418:435–438PubMedCrossRefGoogle Scholar
  53. Ji J, Wernli M, Klimkait T et al (2003) Enhanced gene silencing by the application of multiple specific small interfering RNAs. FEBS Lett 552:247–252PubMedCrossRefGoogle Scholar
  54. Kanda T, Steele R, Ray R et al (2007) Small interfering RNA targeted to hepatitis C virus 5′ nontranslated region exerts potent antiviral effect. J Virol 81:669–676PubMedCrossRefGoogle Scholar
  55. Kandolf R, Klingel K, Zell R et al (1993) Molecular pathogenesis of enterovirus-induced myocarditis: virus persistence and chronic inflammation. Intervirology 35:140–151PubMedGoogle Scholar
  56. Kapadia S, Brideau-Andersen A, Chisari F (2003) Interference of hepatitis C virus RNA replication by short interfering RNAs. Proc Natl Acad Sci USA 100:2014–2018PubMedCrossRefGoogle Scholar
  57. Kartasheva N, Contente A, Lenz-Stoppler C et al (2002) P53 induces the expression of its antagonist p73 delta N, establishing an autoregulatory feedback loop. Oncogene 21:4715–4727PubMedCrossRefGoogle Scholar
  58. Kennerdell J, Carthew R (1998) Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95:1017–1026PubMedCrossRefGoogle Scholar
  59. Khvorova A, Reynolds A, Jayasena S (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115:209–216PubMedCrossRefGoogle Scholar
  60. Kim J, Chung S, Hwang H et al (2007) Expression of short hairpin RNAs against the coxsackievirus B3 exerts potential antiviral effects in COS-7 cells and in mice. Virus Res 125:9–13PubMedCrossRefGoogle Scholar
  61. Knowlton K, Badorff C (1999) The immune system in viral myocarditis: maintaining the balance. Circ Res 85:559–561PubMedGoogle Scholar
  62. Krönke J, Kittler R, Buchholz F et al (2004) Alternative approaches for efficient inhibition of hepatitis C virus replication by small interfering RNAs. J Virol 78:3436–3446PubMedCrossRefGoogle Scholar
  63. Lassus P, Opitz-Araya X, Lazebnik Y (2002) Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science 297:1352–1354PubMedCrossRefGoogle Scholar
  64. Layzer J, McCaffrey A, Tanner A et al (2004) In vivo activity of nuclease-resistant siRNAs. RNA 10:766–771PubMedCrossRefGoogle Scholar
  65. Lee NS, Dohjima T, Bauer G et al (2002) Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol 20:500–505PubMedGoogle Scholar
  66. Lee MT, Coburn G, McClure M et al (2003) Inhibition of human immunodeficiency virus type 1 replication in primary macrophages by using Tat- or CCR5-specific small interfering RNAs expressed from a lentivirus virus. J Virol 77:11964–11972PubMedCrossRefGoogle Scholar
  67. Li M, Kim J, Li S et al (2005) Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy. Mol Ther 12:900–909PubMedCrossRefGoogle Scholar
  68. Luo K, Chang D (2004) The gene-silencing efficiency of siRNA is strongly dependent on the local structure of mRNA at the targeted region. Biochem Biophys Res Commun 318:303–310PubMedCrossRefGoogle Scholar
  69. McCaffrey A, Meuse L, Pham T et al (2002) RNA interference in adult mice. Nature 418:38–39PubMedCrossRefGoogle Scholar
  70. McCaffrey A, Nakai H, Pandey K et al (2003) Inhibition of hepatitis B virus in mice by RNA interference. Nat Biotechnol 21:639–644PubMedCrossRefGoogle Scholar
  71. McCown M, Diamond M, Pekosz A (2003) The utility of siRNA transcripts produced by RNA polymerase I in down regulating viral gene expression and replication of negative- and positive-strand RNA viruses. Virology 313:514–524PubMedCrossRefGoogle Scholar
  72. Merl S, Wessely R (2007) Anti-coxsackieviral efficacy of RNA interference is highly dependent on genomic target selection and emergence of escape mutants. Oligonucleotides 17:44–53PubMedCrossRefGoogle Scholar
  73. Merl S, Michaelis C, Jaschke B et al (2005) Targeting 2A protease by RNA interference attenuates coxsackievirale cytopathogenicity and promotes survival in highly susceptible mice. Circulation 111:1583–1592PubMedCrossRefGoogle Scholar
  74. Miyagishi M, Taira K (2002) U6 promoter-driven siRNAs with four uridine 3′ overhangs efficiently suppress targeted gene expression in mammalian cells. Nat Biotechnol 20:497–500PubMedCrossRefGoogle Scholar
  75. Morrissey D, Blanchard K, Shaw L et al (2005a) Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41:1349–1356PubMedCrossRefGoogle Scholar
  76. Morrissey D, Lockridge J, Shaw L et al (2005b) Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23:1002–1007PubMedCrossRefGoogle Scholar
  77. Muller U, Steinhoff U, Reis L et al (1994) Functional role of type I and type II interferons in antiviral defense. Science 264:1918–1921PubMedCrossRefGoogle Scholar
  78. Novina C, Murray M, Dykxhoorn D et al (2002) siRNA-directed inhibition of HIV-1 infection. Nat Med 8:681–686PubMedGoogle Scholar
  79. Omi K, Tokunaga K, Hohjoh H (2004) Long-lasting RNAi activity in mammalian neurons. FEBS Lett 558:89–95PubMedCrossRefGoogle Scholar
  80. Palauqui J, Vaucheret H (1998) Transgenes are dispensable for the RNA degradation step of cosuppression. Proc Natl Acad Sci USA 95:9675–9680PubMedCrossRefGoogle Scholar
  81. Palliser D, Chowdhury D, Wang Q et al (2006) An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature 439:89–94PubMedCrossRefGoogle Scholar
  82. Park W, Hayafune M, Miyano-Kurosaki N et al (2003) Specific HIV-1 env gene silencing by small interfering RNAs in human peripheral blood mononuclear cells. Gene Ther 10:2046–2050PubMedCrossRefGoogle Scholar
  83. Paul C, Good P, Winer I et al (2002) Effective expression of small interfering RNA in human cells. Nat Biotechnol 20:505–508PubMedCrossRefGoogle Scholar
  84. Prabhu R, Garry R, Dash S (2006) Small interfering RNA targeted to stem–loop II of the 5′ untranslated region effectively inhibits expression of six HCV genotypes. Virol J 3:100PubMedCrossRefGoogle Scholar
  85. Qin X, An D, Chen I et al (2003) Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci USA 100:183–188PubMedCrossRefGoogle Scholar
  86. Randall G, Rice C (2004) Interfering with hepatitis C virus RNA replication. Virus Res 102:19–25PubMedCrossRefGoogle Scholar
  87. Reynolds A, Leake D, Boese Q et al (2004) Rational siRNA design for RNA interference. Nat Biotechnol 22:326–330PubMedCrossRefGoogle Scholar
  88. Rodriguez-Lebron E, Gonzalez-Alegre P (2006) Silencing neurodegenerative disease: bringing RNA interference to the clinic. Expert Rev Neurother 6:223–233PubMedCrossRefGoogle Scholar
  89. Rossi J (2006) RNAi as a treatment for HIV-1 infection. Biotechniques 40(Suppl):25–29CrossRefGoogle Scholar
  90. Rubinson D, Dillon C, Kwiatkowski A et al (2003) A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet 33:401–406PubMedCrossRefGoogle Scholar
  91. Schubert S, Grunert H, Zeichhardt H et al (2005) Maintaining inhibition: siRNA double expression vectors against coxsackieviral RNAs. J Mol Biol 346:457–465PubMedCrossRefGoogle Scholar
  92. Schwarz D, Hutvanger G, Du T et al (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199–208PubMedCrossRefGoogle Scholar
  93. Shankar P, Manjunath N, Lieberman J (2005) The prospect of silencing disease using RNA interference. JAMA 293:1367–1373PubMedCrossRefGoogle Scholar
  94. Shlomai A, Shaul Y (2003) Inhibition of hepatitis B virus expression and replication by RNA interference. Hepatology 37:764–770PubMedCrossRefGoogle Scholar
  95. Stark G, Kerr I, Williams B, Silvermann R et al (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264PubMedCrossRefGoogle Scholar
  96. Stein P, Svoboda P, Anger M et al (2003) RNAi: mammalian oocytes do it without RNA-dependent RNA polymerase. RNA 9:187–192PubMedCrossRefGoogle Scholar
  97. Thomas C, Ehrhardt A, Kay M (2003) Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet 4:346–358PubMedCrossRefGoogle Scholar
  98. Tompkins S, Lo C, Tumpey T et al (2004) Protection against lethal influenza virus challenge by RNA interference in vivo. Proc Natl Acad Sci USA 101:8682–8686PubMedCrossRefGoogle Scholar
  99. Tuschl T, Borkhardt A (2002) Small interfering RNAs: a revolutionary tool for the analysis of gene function and gene therapy. Mol Interv 2:158–167PubMedCrossRefGoogle Scholar
  100. Vickers T, Koo S, Bennett C et al (2003) Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agent. J Biol Chem 278:7108–7118PubMedCrossRefGoogle Scholar
  101. Voinnet O, Vain P, Angell S et al (1998) Systemic spread of sequence-specific transgene RNA degradation in plants is initiated by localized introduction of ectopic promoterless DNA. Cell 95:177–187PubMedCrossRefGoogle Scholar
  102. Wang Q, Contag C, Ilves H et al (2005) Small hairpin RNAs efficiently inhibit hepatitis C IRES-mediated gene expression in human tissue culture cells and a mouse model. Mol Ther 12:562–568PubMedCrossRefGoogle Scholar
  103. Werk D, Schubert S, Lindig V et al (2005) Developing an effective RNA interference strategy against a plus-strand RNA virus: silencing of coxsackievirus B3 and its cognate coxsackievirus-adenovirus receptor. Biol Chem 386:857–863PubMedCrossRefGoogle Scholar
  104. Wessely R, Henke A, Zell R et al (1998a) Low-level expression of a mutant coxsackieviral cDNA induces a myocytopathic effect in culture: an approach to the study of enteroviral persistence in cardiac myocytes. Circulation 98:450–457PubMedGoogle Scholar
  105. Wessely R, Klingel K, Santana L et al (1998b) Transgenic expression of replication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy. J Clin Invest 102:1444–1453PubMedCrossRefGoogle Scholar
  106. Wessely R, Klingel K, Knowlton K et al (2001) Cardioselective infection with coxsackievirus B3 requires intact type I interferon signaling: implications for mortality and early viral replication. Circulation 103:756–761PubMedGoogle Scholar
  107. Wilson J, Jayasena S, Khvorova A et al (2003) RNA interference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells. Proc Natl Acad Sci USA 100:2783–2788PubMedCrossRefGoogle Scholar
  108. Woodruff J (1980) Viral myocarditis. A review. Am J Pathol 101:425–484PubMedGoogle Scholar
  109. Yang S, Tutton S, Pierce E et al (2001) Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells. Mol Cell Biol 21:7807–7816PubMedCrossRefGoogle Scholar
  110. Ying C, DeClercq E, Neyts J (2003) Selective inhibition of hepatitis B virus replication by RNA interference. Biochem Biophys Res Commun 309:482–484PubMedCrossRefGoogle Scholar
  111. Yokota T, Sakamoto N, Enomoto N et al (2003) Inhibition of intracellular hepatitis C virus replication by synthetic and vector-derived small interfering RNAs. EMBO Rep 4:602–608PubMedCrossRefGoogle Scholar
  112. Yoshinari K, Miyagishi M, Taira K (2004) Effects on RNAi of the tight structure, sequence and position of the targeted region. Nucleic Acids Res 32:691–699PubMedCrossRefGoogle Scholar
  113. Yu J, DeRuiter S, Turner D (2002) RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci USA 99:6047–6052PubMedCrossRefGoogle Scholar
  114. Yuan J, Cheung P, Zhang H et al (2005) Inhibition of coxsackievirus B3 replication by small interfering RNAs requires perfect sequence match in the central region of the viral positive strand. J Virol 79:2151–2159PubMedCrossRefGoogle Scholar
  115. Zaragoza C, Ocampo C, Saura M et al (1999) Inducible nitric oxide synthase protection against coxsackievirus pancreatitis. J Immunol 163:5497–5504PubMedGoogle Scholar
  116. Zhang W, Yang H, Kong X et al (2005) Inhibition of respiratory syncytial virus infection with intranasal nanoparticles targeting the viral NS1 gene. Nat Med 11:56–62PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  1. 1.Deutsches Herzzentrum and 1 Medizinische KlinikTechnische UniversitätMünchenGermany

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