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BioMed Research International / 2006 / Article
Special Issue

RNA Interference

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Review Article | Open Access

Volume 2006 |Article ID 071659 | https://doi.org/10.1155/JBB/2006/71659

Achim Aigner, "Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo", BioMed Research International, vol. 2006, Article ID 071659, 15 pages, 2006. https://doi.org/10.1155/JBB/2006/71659

Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo

Achim Aigner1

1Department of Pharmacology and Toxicology, Philipps-University Marburg, Karl-v.-Frisch-Strasse 1, Marburg 35033, Germany

Received14 Jan 2006
Accepted27 Feb 2006
Published18 May 2006

Abstract

RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described.

References

  1. M L Stephenson and P C Zamecnik, “Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 75, no. 1, pp. 285–288, 1978. View at: Google Scholar
  2. P C Zamecnik and M L Stephenson, “Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 75, no. 1, pp. 280–284, 1978. View at: Google Scholar
  3. T R Cech, A J Zaug, and P J Grabowski, “In vitro splicing of the ribosomal RNA precursor of Tetrahymena: involvement of a guanosine nucleotide in the excision of the intervening sequence,” Cell, vol. 27, no. 3 pt 2, pp. 487–496, 1981. View at: Google Scholar
  4. K Kruger, P J Grabowski, A J Zaug, J Sands, D E Gottschling, and T R Cech, “Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena,” Cell, vol. 31, no. 1, pp. 147–157, 1982. View at: Google Scholar
  5. C Guerrier-Takada, K Gardiner, T Marsh, N Pace, and S Altman, “The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme,” Cell, vol. 35, no. 3 pt 2, pp. 849–857, 1983. View at: Google Scholar
  6. A Fire, S Xu, M K Montgomery, S A Kostas, S E Driver, and C C Mello, “Potent and specific genetic interference by double-stranded RNA in caenorhabditis elegans,” Nature, vol. 391, no. 6669, pp. 806–811, 1998. View at: Google Scholar
  7. R Jorgensen, “Altered gene expression in plants due to trans interactions between homologous genes,” Trends in Biotechnology, vol. 8, no. 12, pp. 340–344, 1990. View at: Google Scholar
  8. S Guo and K J Kemphues, “par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed,” Cell, vol. 81, no. 4, pp. 611–620, 1995. View at: Google Scholar
  9. A J Hamilton and D C Baulcombe, “A species of small antisense RNA in posttranscriptional gene silencing in plants,” Science, vol. 286, no. 5441, pp. 950–952, 1999. View at: Google Scholar
  10. P D Zamore, T Tuschl, P A Sharp, and D P Bartel, “RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals,” Cell, vol. 101, no. 1, pp. 25–33, 2000. View at: Google Scholar
  11. E Bernstein, A A Caudy, S M Hammond, and G J Hannon, “Role for a bidentate ribonuclease in the initiation step of RNA interference,” Nature, vol. 409, no. 6818, pp. 363–366, 2001. View at: Google Scholar
  12. S M Elbashir, W Lendeckel, and T Tuschl, “RNA interference is mediated by 21- and 22-nucleotide RNAs,” Genes and Development, vol. 15, no. 2, pp. 188–200, 2001. View at: Google Scholar
  13. S M Hammond, E Bernstein, D Beach, and G J Hannon, “An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells,” Nature, vol. 404, no. 6775, pp. 293–296, 2000. View at: Google Scholar
  14. R E Collins and X Cheng, “Structural domains in RNAi,” FEBS Letters, vol. 579, no. 26, pp. 5841–5849, 2005. View at: Google Scholar
  15. A Nykänen, B Haley, and P D Zamore, “ATP requirements and small interfering RNA structure in the RNA interference pathway,” Cell, vol. 107, no. 3, pp. 309–321, 2001. View at: Google Scholar
  16. S M Elbashir, J Harborth, K Weber, and T Tuschl, “Analysis of gene function in somatic mammalian cells using small interfering RNAs,” Methods, vol. 26, no. 2, pp. 199–213, 2002. View at: Google Scholar
  17. S M Elbashir, J Martinez, A Patkaniowska, W Lendeckel, and T Tuschl, “Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate,” The EMBO Journal, vol. 20, no. 23, pp. 6877–6888, 2001. View at: Google Scholar
  18. T Holen, M Amarzguioui, M T Wiiger, E Babaie, and H Prydz, “Positional effects of short interfering RNAs targeting the human coagulation trigger Tissue Factor,” Nucleic Acids Research, vol. 30, no. 8, pp. 1757–1766, 2002. View at: Google Scholar
  19. D-H Kim, M A Behlke, S D Rose, M-S Chang, S Choi, and J J Rossi, “Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy,” Nature Biotechnology, vol. 23, no. 2, pp. 222–226, 2005. View at: Google Scholar
  20. A Reynolds, D Leake, Q Boese, S Scaringe, W S Marshall, and A Khvorova, “Rational siRNA design for RNA interference,” Nature Biotechnology, vol. 22, no. 3, pp. 326–330, 2004. View at: Google Scholar
  21. H Donis-Keller, “Site specific enzymatic cleavage of RNA,” Nucleic Acids Research, vol. 7, no. 1, pp. 179–192, 1979. View at: Google Scholar
  22. E A Bohula, A J Salisbury, M Sohail et al., “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,” Journal of Biological Chemistry, vol. 278, no. 18, pp. 15991–15997, 2003. View at: Google Scholar
  23. N S Lee, T Dohjima, G Bauer et al., “Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells,” Nature Biotechnology, vol. 20, no. 5, pp. 500–505, 2002. View at: Google Scholar
  24. Y Ding and C E Lawrence, “A statistical sampling algorithm for RNA secondary structure prediction,” Nucleic Acids Research, vol. 31, no. 24, pp. 7280–7301, 2003. View at: Google Scholar
  25. T A Vickers, S Koo, C F Bennett, S T Crooke, N M Dean, and B F Baker, “Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. A comparative analysis,” Journal of Biological Chemistry, vol. 278, no. 9, pp. 7108–7118, 2003. View at: Google Scholar
  26. Y Xu, H-Y Zhang, D Thormeyer et al., “Effective small interfering RNAs and phosphorothioate antisense DNAs have different preferences for target sites in the luciferase mRNAs,” Biochemical and Biophysical Research Communications, vol. 306, no. 3, pp. 712–717, 2003. View at: Google Scholar
  27. R Kretschmer-Kazemi Far and G Sczakiel, “The activity of siRNA in mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides,” Nucleic Acids Research, vol. 31, no. 15, pp. 4417–4424, 2003. View at: Google Scholar
  28. P Sandy, A Ventura, and T Jacks, “Mammalian RNAi: a practical guide,” BioTechniques, vol. 39, no. 2, pp. 215–224, 2005. View at: Google Scholar
  29. A L Jackson, S R Bartz, J Schelter et al., “Expression profiling reveals off-target gene regulation by RNAi,” Nature Biotechnology, vol. 21, no. 6, pp. 635–637, 2003. View at: Google Scholar
  30. V Hornung, M Guenthner-Biller, C Bourquin et al., “Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7,” Nature Medicine, vol. 11, no. 3, pp. 263–270, 2005. View at: Google Scholar
  31. C A Sledz, M Holko, M J De Veer, R H Silverman, and B R-G Williams, “Activation of the interferon system by short-interfering RNAs,” Nature Cell Biology, vol. 5, no. 9, pp. 834–839, 2003. View at: Google Scholar
  32. A J Bridge, S Pebernard, A Ducraux, A-L Nicoulaz, and R Iggo, “Induction of an interferon response by RNAi vectors in mammalian cells,” Nature Genetics, vol. 34, no. 3, pp. 263–264, 2003. View at: Google Scholar
  33. S M Elbashir, J Harborth, W Lendeckel, A Yalcin, K Weber, and T Tuschl, “Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells,” Nature, vol. 411, no. 6836, pp. 494–498, 2001. View at: Google Scholar
  34. N J Caplen, S Parrish, F Imani, A Fire, and R A Morgan, “Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 17, pp. 9742–9747, 2001. View at: Google Scholar
  35. A D Judge, V Sood, J R Shaw, D Fang, K McClintock, and I MacLachlan, “Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA,” Nature Biotechnology, vol. 23, no. 4, pp. 457–462, 2005. View at: Google Scholar
  36. D-H Kim, M Longo, Y Han, P Lundberg, E Cantin, and J J Rossi, “Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase,” Nature Biotechnology, vol. 22, no. 3, pp. 321–325, 2004. View at: Google Scholar
  37. S Lehrman, “Virus treatment questioned after gene therapy death,” Nature, vol. 401, no. 6753, pp. 517–518, 1999. View at: Google Scholar
  38. Q Liu and D A Muruve, “Molecular basis of the inflammatory response to adenovirus vectors,” Gene Therapy, vol. 10, no. 11, pp. 935–940, 2003. View at: Google Scholar
  39. J Y Sun, V Anand-Jawa, S Chatterjee, and K K Jr Wong, “Immune responses to adeno-associated virus and its recombinant vectors,” Gene Therapy, vol. 10, no. 11, pp. 964–976, 2003. View at: Google Scholar
  40. R E Donahue, S W Kessler, D Bodine et al., “Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer,” Journal of Experimental Medicine, vol. 176, no. 4, pp. 1125–1135, 1992. View at: Google Scholar
  41. T Merdan, J Kopeček, and T Kissel, “Prospects for cationic polymers in gene and oligonucleotide therapy against cancer,” Advanced Drug Delivery Reviews, vol. 54, no. 5, pp. 715–758, 2002. View at: Google Scholar
  42. N Duzgunes, C T De Ilarduya, S Simoes, R I Zhdanov, K Konopka, and M C Pedroso de Lima, “Cationic liposomes for gene delivery: novel cationic lipids and enhancement by proteins and peptides,” Current Medicinal Chemistry, vol. 10, no. 14, pp. 1213–1220, 2003. View at: Google Scholar
  43. D Liu, T Ren, and X Gao, “Cationic transfection lipids,” Current Medicinal Chemistry, vol. 10, no. 14, pp. 1307–1315, 2003. View at: Google Scholar
  44. H-F Zhao, D L'Abbé, N Jolicoeur et al., “High-throughput screening of effective siRNAs from RNAi libraries delivered via bacterial invasion,” Nature Methods, vol. 2, no. 12, pp. 967–973, 2005. View at: Google Scholar
  45. W T Godbey, K K Wu, and G A Mikos, “Size matters: molecular weight affects the efficiency of poly(ethylenimine) as a gene delivery vehicle,” Journal of Biomedical Materials Research, vol. 45, no. 3, pp. 268–275, 1999. View at: Google Scholar
  46. M X Tang and F C Szoka, “The influence of polymer structure on the interactions of cationic polymers with DNA and morphology of the resulting complexes,” Gene Therapy, vol. 4, no. 8, pp. 823–832, 1997. View at: Google Scholar
  47. T Bieber and H-P Elsässer, “Preparation of a low molecular weight polyethylenimine for efficient cell transfection,” BioTechniques, vol. 30, no. 1, pp. 74–77, 80–81, 2001. View at: Google Scholar
  48. O Boussif, F Lezoualc'h, M A Zanta et al., “A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 16, pp. 7297–7301, 1995. View at: Google Scholar
  49. J P Behr, “The proton sponge: a trick to enter cells the viruses did not exploit,” Chimia, vol. 51, pp. 34–36, 1997. View at: Google Scholar
  50. M Neu, D Fischer, and T Kissel, “Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives,” Journal of Gene Medicine, vol. 7, no. 8, pp. 992–1009, 2005. View at: Google Scholar
  51. A Kichler, “Gene transfer with modified polyethylenimines,” Journal of Gene Medicine, vol. 6, no. suppl 1, pp. S3–S10, 2004. View at: Google Scholar
  52. E Wagner, R Kircheis, and G F Walker, “Targeted nucleic acid delivery into tumors: new avenues for cancer therapy,” Biomedicine and Pharmacotherapy, vol. 58, no. 3, pp. 152–161, 2004. View at: Google Scholar
  53. P Marschall, N Malik, and Z Larin, “Transfer of YACs up to 2.3 Mb intact into human cells with polyethylenimine,” Gene Therapy, vol. 6, no. 9, pp. 1634–1637, 1999. View at: Google Scholar
  54. B Abdallah, A Hassan, C Benoist, D Goula, J P Behr, and B A Demeneix, “A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: polyethylenimine,” Human Gene Therapy, vol. 7, no. 16, pp. 1947–1954, 1996. View at: Google Scholar
  55. A Boletta, A Benigni, J Lutz, G Remuzzi, M R Soria, and L Monaco, “Nonviral gene delivery to the rat kidney with polyethylenimine,” Human Gene Therapy, vol. 8, no. 10, pp. 1243–1251, 1997. View at: Google Scholar
  56. D Goula, C Benoist, S Mantero, G Merlo, G Levi, and B A Demeneix, “Polyethylenimine-based intravenous delivery of transgenes to mouse lung,” Gene Therapy, vol. 5, no. 9, pp. 1291–1295, 1998. View at: Google Scholar
  57. Y-K Oh, D Suh, J M Kim, H-G Choi, K Shin, and J J Ko, “Polyethylenimine-mediated cellular uptake, nucleus trafficking and expression of cytokine plasmid DNA,” Gene Therapy, vol. 9, no. 23, pp. 1627–1632, 2002. View at: Google Scholar
  58. S Ferrari, A Pettenazzo, N Garbati, F Zacchello, J-P Behr, and M Scarpa, “Polyethylenimine shows properties of interest for cystic fibrosis gene therapy,” Biochimica et Biophysica Acta, vol. 1447, no. 2-3, pp. 219–225, 1999. View at: Google Scholar
  59. W T Godbey, M A Barry, P Saggau, K K Wu, and A G Mikos, “Poly(ethylenimine)-mediated transfection: a new paradigm for gene delivery,” Journal of Biomedical Materials Research, vol. 51, no. 3, pp. 321–328, 2000. View at: Google Scholar
  60. D Fischer, T Bieber, Y Li, H-P Elsässer, and T Kissel, “A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity,” Pharmaceutical Research, vol. 16, no. 8, pp. 1273–1279, 1999. View at: Google Scholar
  61. D Fischer, R Bhattacharya, B Osburg, and U Bickel, “Inhibition of monocyte adhesion on brain-derived endothelial cells by NF-kappaB decoy/polyethylenimine complexes,” Journal of Gene Medicine, vol. 7, no. 8, pp. 1063–1076, 2005. View at: Google Scholar
  62. D Fischer, Y Li, B Ahlemeyer, J Krieglstein, and T Kissel, “In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis,” Biomaterials, vol. 24, no. 7, pp. 1121–1131, 2003. View at: Google Scholar
  63. K Kunath, A von Harpe, D Fischer et al., “Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine,” Journal of Controlled Release, vol. 89, no. 1, pp. 113–125, 2003. View at: Google Scholar
  64. M Ogris, P Steinlein, M Kursa, K Mechtler, R Kircheis, and E Wagner, “The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells,” Gene Therapy, vol. 5, no. 10, pp. 1425–1433, 1998. View at: Google Scholar
  65. L Wightman, R Kircheis, V Rössler et al., “Different behavior of branched and linear polyethylenimine for gene delivery in vitro and in vivo,” Journal of Gene Medicine, vol. 3, no. 4, pp. 362–372, 2001. View at: Google Scholar
  66. U Lungwitz, M Breunig, T Blunk, and A Göpferich, “Polyethylenimine-based non-viral gene delivery systems,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 60, no. 2, pp. 247–266, 2005. View at: Google Scholar
  67. A Eigner, D Fischer, T Merdan, C Brus, T Kissel, and F Czubayko, “Delivery of unmodified bioactive ribozymes by an RNA stabilizing polyethylenimine LMW PEI efficiently down regulates gene expression,” Gene Therapy, vol. 9, no. 24, pp. 1700–1707, 2002. View at: Google Scholar
  68. C Brus, H Petersen, A Aigner, F Czubayco, and T Kissel, “Physicochemical and biological characterization of polyethylenimine-graft- poly(ethylene glycol) block copolymers as a delivery system for oligonucleotides and ribozymes,” Bioconjugate Chemistry, vol. 15, no. 4, pp. 677–684, 2004. View at: Google Scholar
  69. C Brus, H Petersen, A Aigner, F Czubayko, and T Kissel, “Efficiency of polyethylenimines and polyethylenimine-graft-poly (ethylene glycol) block copolymers to protect oligonucleotides against enzymatic degradation,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 57, no. 3, pp. 427–430, 2004. View at: Google Scholar
  70. B Urban-Klein, S Werth, S Abuharbeid, F Czubayko, and A Aigner, “RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo,” Gene Therapy, vol. 12, no. 5, pp. 461–466, 2005. View at: Google Scholar
  71. Z Hassani, G F Lemkine, P Erbacher et al., “Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels,” Journal of Gene Medicine, vol. 7, no. 2, pp. 198–207, 2005. View at: Google Scholar
  72. C Brus, E Kleemann, A Aigner, F Czubayko, and T Kissel, “Stabilization of oligonucleotide-polyethylenimine complexes by freeze-drying: physicochemical and biological characterization,” Journal of Controlled Release, vol. 95, no. 1, pp. 119–131, 2004. View at: Google Scholar
  73. R M Schiffelers, A Ansari, J Xu et al., “Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle,” Nucleic Acids Research, vol. 32, no. 19, p. e149, 2004. View at: Google Scholar
  74. Q Ge, L Filip, A Bai, T Nguyen, H N Eisen, and J Chen, “Inhibition of influenza virus production in virus-infected mice by RNA interference,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 23, pp. 8676–8681, 2004. View at: Google Scholar
  75. D J Slamon, W Godolphin, L A Jones et al., “Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer,” Science, vol. 244, no. 4905, pp. 707–712, 1989. View at: Google Scholar
  76. H Juhl, S G Downing, A Wellstein, and F Czubayko, “HER-2/neu is rate-limiting for ovarian cancer growth. Conditional depletion of HER-2/neu by ribozyme targeting,” Journal of Biological Chemistry, vol. 272, no. 47, pp. 29482–29486, 1997. View at: Google Scholar
  77. A Thybusch-Bernhardt, A Aigner, S Beckmann, F Czubayko, and H Juhl, “Ribozyme targeting of HER-2 inhibits pancreatic cancer cell growth in vivo,” European Journal of Cancer, vol. 37, no. 13, pp. 1688–1694, 2001. View at: Google Scholar
  78. T Suzuki, B Anderegg, T Ohkawa et al., “Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells,” Gene Therapy, vol. 7, no. 3, pp. 241–248, 2000. View at: Google Scholar
  79. F Czubayko, S G Downing, S S Hsieh et al., “Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation,” Gene Therapy, vol. 4, no. 9, pp. 943–949, 1997. View at: Google Scholar
  80. A Choudhury, J Charo, S K Parapuram et al., “Small interfering RNA (siRNA) inhibits the expression of the Her2/Neu gene, upregulates HLA class I and induces apoptosis of Her2/Neu positive tumor cell lines,” International Journal of Cancer, vol. 108, no. 1, pp. 71–77, 2004. View at: Google Scholar
  81. G Yang, K Q Cai, J A Thompson-Lanza, R C Jr Bast, and J Liu, “Inhibition of breast and ovarian tumor growth through multiple signaling pathways by using retrovirus-mediated small interfering RNA against Her-2/neu gene expression,” Journal of Biological Chemistry, vol. 279, no. 6, pp. 4339–4345, 2004. View at: Google Scholar
  82. F Czubayko, E DE Liaudet-Coopman, A Aigner, A T Tuveson, G Berchem, and A Wellstein, “A secreted FGF-binding protein can serve as the angiogenic switch in human cancer,” Nature Medicine, vol. 3, no. 10, pp. 1137–1140, 1997. View at: Google Scholar
  83. A Aigner, H Renneberg, J Bojunga, J Apel, P S Nelson, and F Czubayko, “Ribozyme-targeting of a secreted FGF-binding protein (FGF-BP) inhibits proliferation of prostate cancer cells in vitro and in vivo,” Oncogene, vol. 21, no. 37, pp. 5733–5742, 2002. View at: Google Scholar
  84. S Abuharbeid, F Czubayko, and A Aigner, “The fibroblast growth factor-binding protein FGF-BP,” to appear in The International Journal of Biochemistry & Cell Biology. View at: Google Scholar
  85. W J Fang, N Hartmann, D Chow, A T Riegel, and A Wellstein, “Pleiotrophin stimulates fibroblasts and endothelial and epithelial cells and is expressed in human cancer,” Journal of Biological Chemistry, vol. 267, no. 36, pp. 25889–25897, 1992. View at: Google Scholar
  86. E T Bowden, G E Stoica, and A Wellstein, “Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase,” Journal of Biological Chemistry, vol. 277, no. 39, pp. 35862–35868, 2002. View at: Google Scholar
  87. A Wellstein, W J Fang, A Khatri et al., “A heparin-binding growth factor secreted from breast cancer cells homologous to a developmentally regulated cytokine,” Journal of Biological Chemistry, vol. 267, no. 4, pp. 2582–2587, 1992. View at: Google Scholar
  88. P G Milner, Y S Li, R M Hoffman, C M Kodner, N R Siegel, and T F Deuel, “A novel 17 kD heparin-binding growth factor (HBGF-8) in bovine uterus: purification and N-terminal amino acid sequence,” Biochemical and Biophysical Research Communications, vol. 165, no. 3, pp. 1096–1103, 1989. View at: Google Scholar
  89. N Zhang, R Zhong, Z Y Wang, and T F Deuel, “Human breast cancer growth inhibited in vivo by a dominant negative pleiotrophin mutant,” Journal of Biological Chemistry, vol. 272, no. 27, pp. 16733–16736, 1997. View at: Google Scholar
  90. F Czubayko, A M Schulte, G J Berchem, and A Wellstein, “Melanoma angiogenesis and metastasis modulated by ribozyme targeting of the secreted growth factor pleiotrophin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 25, pp. 14753–14758, 1996. View at: Google Scholar
  91. F Czubayko, A T Riegel, and A Wellstein, “Ribozyme-targeting elucidates a direct role of pleiotrophin in tumor growth,” Journal of Biological Chemistry, vol. 269, no. 33, pp. 21358–21363, 1994. View at: Google Scholar
  92. A M Schulte, S Lai, A Kurtz, F Czubayko, A T Riegel, and A Wellstein, “Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germ-line insertion of an endogenous retrovirus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 25, pp. 14759–14764, 1996. View at: Google Scholar
  93. R Choudhuri, H-T Zhang, S Donnini, M Ziche, and R Bicknell, “An angiogenic role for the neurokines midkine and pleiotrophin in tumorigenesis,” Cancer Research, vol. 57, no. 9, pp. 1814–1819, 1997. View at: Google Scholar
  94. L Zender, S Hütker, C Liedtke et al., “Caspase 8 small interfering RNA prevents acute liver failure in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 13, pp. 7797–7802, 2003. View at: Google Scholar
  95. H Giladi, M Ketzinel-Gilad, L Rivkin, Y Felig, O Nussbaum, and E Galun, “Small interfering RNA inhibits hepatitis B virus replication in mice,” Molecular Therapy, vol. 8, no. 5, pp. 769–776, 2003. View at: Google Scholar
  96. C Klein, C T Bock, H Wedemeyer et al., “Inhibition of hepatitis B virus replication in vivo by nucleoside analogues and siRNA,” Gastroenterology, vol. 125, no. 1, pp. 9–18, 2003. View at: Google Scholar
  97. D L Lewis, J E Hagstrom, A G Loomis, J A Wolff, and H Herweijer, “Efficient delivery of siRNA for inhibition of gene expression in postnatal mice,” Nature Genetics, vol. 32, no. 1, pp. 107–108, 2002. View at: Google Scholar
  98. E Song, S-K Lee, J Wang et al., “RNA interference targeting Fas protects mice from fulminant hepatitis,” Nature Medicine, vol. 9, no. 3, pp. 347–351, 2003. View at: Google Scholar
  99. J D Heidel, S Hu, X F Liu, T J Triche, and M E Davis, “Lack of interferon response in animals to naked siRNAs,” Nature Biotechnology, vol. 22, no. 12, pp. 1579–1582, 2004. View at: Google Scholar
  100. Y Matsui, N Kobayashi, M Nishikawa, and Y Takakura, “Sequence-specific suppression of mdr1a/1b expression in mice via RNA interference,” Pharmaceutical Research, vol. 22, no. 12, pp. 2091–2098, 2005. View at: Google Scholar
  101. J L Contreras, M Vilatoba, C Eckstein, G Bilbao, J Anthony Thompson, and D E Eckhoff, “Caspase-8 and caspase-3 small interfering RNA decreases ischemia/reperfusion injury to the liver in mice,” Surgery, vol. 136, no. 2, pp. 390–400, 2004. View at: Google Scholar
  102. Y Sato, T Ajiki, S Inoue et al., “Gene silencing in rat-liver and limb grafts by rapid injection of small interference RNA,” Transplantation, vol. 79, no. 2, pp. 240–243, 2005. View at: Google Scholar
  103. Z Liang, Y Yoon, J Votaw, M M Goodman, L Williams, and H Shim, “Silencing of CXCR4 blocks breast cancer metastasis,” Cancer Research, vol. 65, no. 3, pp. 967–971, 2005. View at: Google Scholar
  104. S Merl, C Michaelis, B Jaschke, M Vorpahl, S Seidl, and R Wessely, “Targeting 2A protease by RNA interference attenuates coxsackieviral cytopathogenicity and promotes survival in highly susceptible mice,” Circulation, vol. 111, no. 13, pp. 1583–1592, 2005. View at: Google Scholar
  105. M S Duxbury, E Matros, H Ito, M J Zinner, S W Ashley, and E E Whang, “Systemic siRNA-mediated gene silencing: a new approach to targeted therapy of cancer,” Annals of Surgery, vol. 240, no. 4, pp. 667–676; discussion 675–676, 2004. View at: Google Scholar
  106. M S Duxbury, H Ito, M J Zinner, S W Ashley, and E E Whang, “EphA2: a determinant of malignant cellular behavior and a potential therapeutic target in pancreatic adenocarcinoma,” Oncogene, vol. 23, no. 7, pp. 1448–1456, 2004. View at: Google Scholar
  107. M S Duxbury, H Ito, E Benoit, M J Zinner, S W Ashley, and E E Whang, “RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity,” Biochemical and Biophysical Research Communications, vol. 311, no. 3, pp. 786–792, 2003. View at: Google Scholar
  108. P Hamar, E Song, G Kökeny, A Chen, N Ouyang, and J Lieberman, “Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 41, pp. 14883–14888, 2004. View at: Google Scholar
  109. S M Tompkins, C-Y Lo, T M Tumpey, and S L Epstein, “Protection against lethal influenza virus challenge by RNA interference in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 23, pp. 8682–8686, 2004. View at: Google Scholar
  110. S P Bradley, C Rastellini, M A Da Costa et al., “Gene silencing in the endocrine pancreas mediated by short-interfering RNA,” Pancreas, vol. 31, no. 4, pp. 373–379, 2005. View at: Google Scholar
  111. T Hino, T Yokota, S Ito et al., “In vivo delivery of small interfering RNA targeting brain capillary endothelial cells,” Biochemical and Biophysical Research Communications, vol. 340, no. 1, pp. 263–267, 2006. View at: Google Scholar
  112. S Filleur, A Courtin, S Ait-Si-Ali et al., “SiRNA-mediated inhibition of vascular endothelial growth factor severely limits tumor resistance to antiangiogenic thrombospondin-1 and slows tumor vascularization and growth,” Cancer Research, vol. 63, no. 14, pp. 3919–3922, 2003. View at: Google Scholar
  113. M Ocker, D Neureiter, M Lueders et al., “Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic cancer,” Gut, vol. 54, no. 9, pp. 1298–1308, 2005. View at: Google Scholar
  114. P Lingor, P Koeberle, S Kügler, and M Bähr, “Down-regulation of apoptosis mediators by RNAi inhibits axotomy-induced retinal ganglion cell death in vivo,” Brain, vol. 128, no. 3, pp. 550–558, 2005. View at: Google Scholar
  115. J L Lomas-Neira, C-S Chung, D E Wesche, M Perl, and A Ayala, “In vivo gene silencing (with siRNA) of pulmonary expression of MIP-2 versus KC results in divergent effects on hemorrhage-induced, neutrophil-mediated septic acute lung injury,” Journal of Leukocyte Biology, vol. 77, no. 6, pp. 846–853, 2005. View at: Google Scholar
  116. A P McCaffrey, L Meuse, T T Pham, D S Conklin, G J Hannon, and M A Kay, “RNA interference in adult mice,” Nature, vol. 418, no. 6893, pp. 38–39, 2002. View at: Google Scholar
  117. S J Reich, J Fosnot, A Kuroki et al., “Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in mouse model,” Molecular Vision, vol. 9, pp. 210–216, 2003. View at: Google Scholar
  118. R M Schiffelers, J Xu, G Storm, M C Woodle, and P V Scaria, “Effects of treatment with small interfering RNA on joint inflammation in mice with collagen-induced arthritis,” Arthritis and Rheumatism, vol. 52, no. 4, pp. 1314–1318, 2005. View at: Google Scholar
  119. T W Kim, J-H Lee, L He et al., “Modification of professional antigen-presenting cells with small interfering RNA in vivo to enhance cancer vaccine potency,” Cancer Research, vol. 65, no. 1, pp. 309–316, 2005. View at: Google Scholar
  120. V Bitko, A Musiyenko, O Shulyayeva, and S Barik, “Inhibition of respiratory viruses by nasally administered siRNA,” Nature Medicine, vol. 11, no. 1, pp. 50–55, 2005. View at: Google Scholar
  121. X Zhang, P Shan, D Jiang et al., “Small interfering RNA targeting heme oxygenase-1 enhances ischemia-reperfusion-induced lung apoptosis,” Journal of Biological Chemistry, vol. 279, no. 11, pp. 10677–10684, 2004. View at: Google Scholar
  122. B-J Li, Q Tang, D Cheng et al., “Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque,” Nature Medicine, vol. 11, no. 9, pp. 944–951, 2005. View at: Google Scholar
  123. S P Bradley, T F Kowalik, C Rastellini et al., “Successful incorporation of short-interfering RNA into islet cells by in situ perfusion,” Transplantation Proceedings, vol. 37, no. 1, pp. 233–236, 2005. View at: Google Scholar
  124. J-Y Pillé, C Denoyelle, J Varet et al., “Anti-RhoA and anti-RhoC siRNAs inhibit the proliferation and invasiveness of MDA-MB-231 breast cancer cells in vitro and in vivo,” Molecular Therapy, vol. 11, no. 2, pp. 267–274, 2005. View at: Google Scholar
  125. S Aharinejad, P Paulus, M Sioud et al., “Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice,” Cancer Research, vol. 64, no. 15, pp. 5378–5384, 2004. View at: Google Scholar
  126. G Dorn, S Patel, G Wotherspoon et al., “siRNA relieves chronic neuropathic pain,” Nucleic Acids Research, vol. 32, no. 5, p. e49, 2004. View at: Google Scholar
  127. Y Takabatake, Y Isaka, M Mizui et al., “Exploring RNA inteference as a therapeutic strategy for renal disease,” Gene Therapy, vol. 12, no. 12, pp. 965–973, 2005. View at: Google Scholar
  128. M Perl, C-S Chung, J Lomas-Neira et al., “Silencing of Fas, but not caspase-8, in lung epithelial cells ameliorates pulmonary apoptosis, inflammation, and neutrophil influx after hemorrhagic shock and sepsis,” American Journal of Pathology, vol. 167, no. 6, pp. 1545–1559, 2005. View at: Google Scholar
  129. H Makimura, T M Mizuno, J W Mastaitis, R Agami, and C V Mobbs, “Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake,” BMC Neuroscience, vol. 3, no. 1, p. 18, 2002. View at: Google Scholar
  130. D R Thakker, F Natt, D Hüsken et al., “Neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral RNA interference,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 49, pp. 17270–17275, 2004. View at: Google Scholar
  131. D R Thakker, F Natt, D Hüsken et al., “siRNA-mediated knockdown of the serotonin transporter in the adult mouse brain,” Molecular Psychiatry, vol. 10, no. 8, pp. 782–789, 714, 2005. View at: Google Scholar
  132. A S Herard, L Besret, A Dubois et al., “siRNA targeted against amyloid precursor protein impairs synaptic activity in vivo,” to appear in Neurobiology of Aging. View at: Google Scholar
  133. B Kim, Q Tang, P S Biswas et al., “Inhibition of ocular angiogenesis by siRNA targeting vascular endothelial growth factor pathway genes: Therapeutic strategy for herpetic stromal keratitis,” American Journal of Pathology, vol. 165, no. 6, pp. 2177–2185, 2004. View at: Google Scholar
  134. H Nakamura, S S Siddiqui, X Shen et al., “RNA interference targeting transforming growth factor-beta type II receptor suppresses ocular inflammation and fibrosis,” Molecular Vision, vol. 10, pp. 703–711, 2004. View at: Google Scholar
  135. J Yano, K Hirabayashi, S-I Nakagawa et al., “Antitumor activity of small interfering RNA/cationic liposome complex in mouse models of cancer,” Clinical Cancer Research, vol. 10, no. 22, pp. 7721–7726, 2004. View at: Google Scholar
  136. A Hassan, Y Tian, W Zheng, H Ji, K Sandberg, and J G Verbalis, “Small interfering RNA-mediated functional silencing of vasopressin V 2 receptors in the mouse kidney,” Physiological Genomics, vol. 21, no. 3, pp. 382–388, 2005. View at: Google Scholar
  137. C N Jr Landen, A Chavez-Reyes, C Bucana et al., “Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery,” Cancer Research, vol. 65, no. 15, pp. 6910–6918, 2005. View at: Google Scholar
  138. K Miyawaki-Shimizu, D Predescu, J Shimizu, M Broman, S Predescu, and A B Malik, “siRNA-induced caveolin-1 knockdown in mice increases lung vascular permeability via the junctional pathway,” American Journal of Physiology. Lung Cellular and Molecular Physiology, vol. 290, no. 2, pp. L405–L413, 2006. View at: Google Scholar
  139. M Sioud and D R Sørensen, “Cationic liposome-mediated delivery of siRNAs in adult mice,” Biochemical and Biophysical Research Communications, vol. 312, no. 4, pp. 1220–1225, 2003. View at: Google Scholar
  140. M A Flynn, D G Casey, S M Todryk, and B P Mahon, “Efficient delivery of small interfering RNA for inhibition of IL-12p40 expression in vivo,” Journal of Inflammation, vol. 1, no. 1, p. 4, 2004. View at: Google Scholar
  141. U N Verma, R M Surabhi, A Schmaltieg, C Becerra, and R B Gaynor, “Small interfering RNAs directed against beta-catenin inhibit the in vitro and in vivo growth of colon cancer cells,” Clinical Cancer Research, vol. 9, no. 4, pp. 1291–1300, 2003. View at: Google Scholar
  142. D R Sørensen, M Leirdal, and M Sioud, “Gene silencing by systemic delivery of synthetic siRNAs in adult mice,” Journal of Molecular Biology, vol. 327, no. 4, pp. 761–766, 2003. View at: Google Scholar
  143. M Nogawa, T Yuasa, S Kimura et al., “Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer,” Journal of Clinical Investigation, vol. 115, no. 4, pp. 978–985, 2005. View at: Google Scholar
  144. Y Maeda, K Fukushima, K Nishizaki, and R JH Smith, “In vitro and in vivo suppression of GJB2 expression by RNA interference,” Human Molecular Genetics, vol. 14, no. 12, pp. 1641–1650, 2005. View at: Google Scholar
  145. S Fukuyama, I Yoshino, M Yamaguchi et al., “Blockage of the macrophage migration inhibitory factor expression by short interference RNA inhibited the rejection of an allogeneic tracheal graft,” Transplant International, vol. 18, no. 10, pp. 1203–1209, 2005. View at: Google Scholar
  146. K Bollerot, D Sugiyama, V Escriou et al., “Widespread lipoplex-mediated gene transfer to vascular endothelial cells and hemangioblasts in the vertebrate embryo,” Developmental Dynamics, vol. 235, no. 1, pp. 105–114, 2006. View at: Google Scholar
  147. A Pal, A Ahmad, S Khan et al., “Systemic delivery of RafsiRNA using cationic cardiolipin liposomes silences Raf-1 expression and inhibits tumor growth in xenograft model of human prostate cancer,” International Journal of Oncology, vol. 26, no. 4, pp. 1087–1091, 2005. View at: Google Scholar
  148. P-Y Chien, J Wang, D Carbonaro et al., “Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo,” Cancer Gene Therapy, vol. 12, no. 3, pp. 321–328, 2005. View at: Google Scholar
  149. M C Luo, D Q Zhang, S W Ma et al., “An efficient intrathecal delivery of small interfering RNA to the spinal cord and peripheral neurons,” Molecular Pain, vol. 1, p. 29, 2005. View at: Google Scholar
  150. J-R Bertrand, M Pottier, A Vekris, P Opolon, A Maksimenko, and C Malvya, “Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo,” Biochemical and Biophysical Research Communications, vol. 296, no. 4, pp. 1000–1004, 2002. View at: Google Scholar
  151. D Palliser, D Chowdhury, Q-Y Wang et al., “An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection,” Nature, vol. 439, no. 7072, pp. 89–94, 2006. View at: Google Scholar
  152. J Soutschek, A Akinc, B Bramlage et al., “Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs,” Nature, vol. 432, no. 7014, pp. 173–178, 2004. View at: Google Scholar
  153. D V Morrissey, J A Lockridge, L Shaw et al., “Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs,” Nature Biotechnology, vol. 23, no. 8, pp. 1002–1007, 2005. View at: Google Scholar
  154. M Golzio, L Mazzolini, P Moller, M P Rols, and J Teissié, “Inhibition of gene expression in mice muscle by in vivo electrically mediated siRNA delivery,” Gene Therapy, vol. 12, no. 3, pp. 246–251, 2005. View at: Google Scholar
  155. Q Leng and A J Mixson, “Small interfering RNA targeting Raf-1 inhibits tumor growth in vitro and in vivo,” Cancer Gene Therapy, vol. 12, no. 8, pp. 682–690, 2005. View at: Google Scholar
  156. Y Takei, K Kadomatsu, Y Yuzawa, S Matsuo, and T Muramatsu, “A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics,” Cancer Research, vol. 64, no. 10, pp. 3365–3370, 2004. View at: Google Scholar
  157. Y Minakuchi, F Takeshita, N Kosaka et al., “Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo,” Nucleic Acids Research, vol. 32, no. 13, p. e109, 2004. View at: Google Scholar
  158. F Takeshita, Y Minakuchi, S Nagahara et al., “Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 34, pp. 12177–12182, 2005. View at: Google Scholar
  159. M Ito, S Yamamoto, K Nimura, K Hiraoka, K Tamai, and Y Kaneda, “Rad51 siRNA delivered by HVJ envelope vector enhances the anti-cancer effect of cisplatin,” Journal of Gene Medicine, vol. 7, no. 8, pp. 1044–1052, 2005. View at: Google Scholar
  160. E Song, P Zhu, S-K Lee et al., “Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors,” Nature Biotechnology, vol. 23, no. 6, pp. 709–717, 2005. View at: Google Scholar
  161. C Yin, L Xi, X Wang, M Eapen, and R C Kukreja, “Silencing heat shock factor 1 by small interfering RNA abrogates heat shock-induced cardioprotection against ischemia-reperfusion injury in mice,” Journal of Molecular and Cellular Cardiology, vol. 39, no. 4, pp. 681–689, 2005. View at: Google Scholar
  162. J de Jonge, M Holtrop, J Wilschut, and A Huckriede, “Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs,” Gene Therapy, vol. 13, no. 5, pp. 400–411, 2006. View at: Google Scholar

Copyright © 2006 Achim Aigner. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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