Pharmaceutical Research

, Volume 27, Issue 3, pp 400–420 | Cite as

Pseudovirions as Vehicles for the Delivery of siRNA

  • Paul E. Lund
  • Ryan C. Hunt
  • Michael M. Gottesman
  • Chava Kimchi-Sarfaty
Expert Review


Over the last two decades, small interfering RNA (siRNA)-mediated gene silencing has quickly become one of the most powerful techniques used to study gene function in vitro and a promising area for new therapeutics. Delivery remains a significant impediment to realizing the therapeutic potential of siRNA, a problem that is also tied to immunogenicity and toxicity. Numerous delivery vehicles have been developed, including some that can be categorized as pseudovirions: these are vectors that are directly derived from viruses but whose viral coding sequences have been eliminated, preventing their classification as viral vectors. Characteristics of the pseudovirions discussed in this review, namely phagemids, HSV amplicons, SV40 in vitro-packaged vectors, influenza virosomes, and HVJ-Envelope vectors, make them attractive for the delivery of siRNA-based therapeutics. Pseudovirions were shown to deliver siRNA effector molecules and bring about RNA interference (RNAi) in various cell types in vitro, and in vivo using immune-deficient and immune-competent mouse models. Levels of silencing were not always determined directly, but the duration of siRNA-induced knockdown lasted at least 3 days. We present examples of the use of pseudovirions for the delivery of synthetic siRNA as well as the delivery and expression of DNA-directed siRNA.

Key words

pseudoviral delivery vehicle pseudovirion siRNA delivery 



The authors thank George Leiman for his editorial assistance with this manuscript as well as his insightful aide in the preparation of the figures. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and by the Research Participation program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration.


  1. 1.
    Fire A, Xu SQ, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998;391:806–11.PubMedGoogle Scholar
  2. 2.
    Rana TM. Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol. 2007;8:23–36.PubMedGoogle Scholar
  3. 3.
    Sontheimer EJ. Assembly and function of RNA silencing complexes. Nat Rev Mol Cell Biol. 2005;6:127–38.PubMedGoogle Scholar
  4. 4.
    Aigner A. Cellular delivery in vivo of siRNA-based therapeutics. Curr Pharm Des. 2008;14:3603–19.PubMedGoogle Scholar
  5. 5.
    Aigner A. Gene silencing through RNA interference (RNAi) in vivo: strategies based on the direct application of siRNAs. J Biotechnol. 2006;124:12–25.PubMedGoogle Scholar
  6. 6.
    Aigner A. Delivery systems for the direct application of siRNAs to induce RNA interference (RNAi) in vivo. J Biomed Biotechnol. 2006;4:71659.Google Scholar
  7. 7.
    Martin SE, Caplen NJ. Applications of RNA interference in mammalian systems. Annu Rev Genomics Hum Genet. 2007;8:81–108.PubMedGoogle Scholar
  8. 8.
    Nguyen T, Menocal EM, Harborth J, Fruehauf JH. RNAi therapeutics: an update on delivery. Curr Opin Mol Ther. 2008;10:158–67.PubMedGoogle Scholar
  9. 9.
    Sandy P, Ventura A, Jacks T. Mammalian RNAi: a practical guide. Biotechniques. 2005;39:215–24.PubMedGoogle Scholar
  10. 10.
    Sanguino A, Lopez-Berestein G, Sood AK. Strategies for in vivo siRNA delivery in cancer. Mini-Rev Med Chem. 2008;8:248–55.PubMedGoogle Scholar
  11. 11.
    de Fougerolles A. Delivery vehicles for small interfering RNA in vivo. Hum Gene Ther. 2008;19:125–32.PubMedGoogle Scholar
  12. 12.
    Amarzguioui M, Rossi JJ, Kim D. Approaches for chemically synthesized siRNA and vector-mediated RNAi. FEBS Lett. 2005;579:5974–81.PubMedGoogle Scholar
  13. 13.
    Judge A, Maclachlan I. Overcoming the innate immune response to small interfering RNA. Hum Gene Ther. 2008;19:111–24.PubMedGoogle Scholar
  14. 14.
    Behlke MA. Progress towards in vivo use of siRNAs. Mol Ther. 2006;13:644–70.PubMedGoogle Scholar
  15. 15.
    Siolas D, Lerner C, Burchard J, Ge W, Linsley PS, Paddison PJ, et al. Synthetic shRNAs as potent RNAi triggers. Nat Biotechnol. 2005;23:227–31.PubMedGoogle Scholar
  16. 16.
    Dotto GP, Enea V, Zinder ND. Functional analysis of bacteriophage f1 intergenic region. Virology. 1981;114:463–73.PubMedGoogle Scholar
  17. 17.
    Dente L, Cortese R. pEMBL: a new family of single-stranded plasmids for sequencing DNA. Methods Enzymol. 1987;155:111–9.PubMedGoogle Scholar
  18. 18.
    Mead DA, Kemper B. Chimeric single-stranded DNA phage-plasmid cloning vectors. Biotechnology. 1988;10:85–102.PubMedGoogle Scholar
  19. 19.
    Kehoe JW, Kay BK. Filamentous phage display in the new millennium. Chem Rev. 2005;105:4056–72.PubMedGoogle Scholar
  20. 20.
    Marvin DA. Filamentous phage structure, infection and assembly. Curr Opin Struct Biol. 1998;8:150–8.PubMedGoogle Scholar
  21. 21.
    Monaci P, Urbanelli L, Fontana L. Phage as gene delivery vectors. Curr Opin Mol Ther. 2001;3:159–69.PubMedGoogle Scholar
  22. 22.
    Li ZH, Jiang H, Zhang J, Gu JR. Cell-targeted phagemid particles preparation using Escherichia coli bearing ligand-pIII encoding helper phage genome. Biotechniques. 2006;41:706–7.PubMedGoogle Scholar
  23. 23.
    Chasteen L, Ayriss J, Pavlik P, Bradbury ARM. Eliminating helper phage from phage display. Nucleic Acids Res. 2006;34:11.Google Scholar
  24. 24.
    Jiang H, Cai XM, Shi BZ, Zhang J, Li ZH, Gu JR. Development of efficient RNA interference system using EGF-displaying phagemid particles. Acta Pharmacol Sin. 2008;29:437–42.PubMedGoogle Scholar
  25. 25.
    Cai XM, Xie HL, Liu MZ, Zha XL. Inhibition of cell growth and invasion by epidermal growth factor-targeted phagemid particles carrying siRNA against focal adhesion kinase in the presence of hydroxycamptothecin. BMC Biotechnol. 2008;8:7.Google Scholar
  26. 26.
    van Nimwegen MJ, van de Water B. Focal adhesion kinase: A potential target in cancer therapy. Biochem Pharmacol. 2007;73:597–609.PubMedGoogle Scholar
  27. 27.
    Burg MA, Jensen-Pergakes K, Gonzalez AM, Ravey P, Baird A, Larocca D. Enhanced phagemid particle gene transfer in camptothecin-treated carcinoma cells. Cancer Res. 2002;62:977–81.PubMedGoogle Scholar
  28. 28.
    Liang Y, Shi BZ, Zhang J, Jiang H, Xu YH, Li ZH, et al. Better gene expression by (-)gene than by (+)gene in phage gene delivery systems. Biotechnol Prog. 2006;22:626–30.PubMedGoogle Scholar
  29. 29.
    Merril CR, Biswas B, Carlton R, Jensen NC, Creed GJ, Zullo S, et al. Long-circulating bacteriophage as antibacterial agents. Proc Natl Acad Sci USA. 1996;93:3188–92.PubMedGoogle Scholar
  30. 30.
    Molenaar TJM, Michon I, de Haas SAM, van Berkel TJC, Kuiper J, Biessen EAL. Uptake and processing of modified bacteriophage M13 in mice: Implications for phage display. Virology. 2002;293:182–91.PubMedGoogle Scholar
  31. 31.
    Vitiello CL, Merril CR, Adhya S. An amino acid substitution in a capsid protein enhances phage survival in mouse circulatory system more than a 1000-fold. Virus Res. 2005;114:101–3.PubMedGoogle Scholar
  32. 32.
    Yip YL, Hawkins NJ, Smith G, Ward RL. Biodistribution of filamentous phage-Fab in nude mice. J Immunol Methods. 1999;225:171–8.PubMedGoogle Scholar
  33. 33.
    Zou J, Dickerson MT, Owen NK, Landon LA, Deutscher SL. Biodistribution of filamentous phage peptide libraries in mice. Mol Biol Rep. 2004;31:121–9.PubMedGoogle Scholar
  34. 34.
    Kassner PD, Burg MA, Baird A, Larocca D. Genetic selection of phage engineered for receptor-mediated gene transfer to mammalian cells. Biochem Biophys Res Commun. 1999;264:921–8.PubMedGoogle Scholar
  35. 35.
    Larocca D, Baird A. Receptor-mediated gene transfer by phage-display vectors: applications in functional genomics and gene therapy. Drug Discov Today. 2001;6:793–801.PubMedGoogle Scholar
  36. 36.
    Larocca D, Burg MA, Jensen-Pergakes K, Ravey EP, Gonzalez AM, Baird A. Evolving phage vectors for cell targeted gene delivery. Curr Pharm Biotechnol. 2002;3:45–57.PubMedGoogle Scholar
  37. 37.
    Legendre D, Fastrez J. Construction and exploitation in model experiments of functional selection of a landscape library expressed from a phagemid. Gene. 2002;290:203–15.PubMedGoogle Scholar
  38. 38.
    Uppala A, Koivunen E. Targeting of phage display vectors to mammalian cells. Comb Chem High Throughput Screen. 2000;3:373–92.PubMedGoogle Scholar
  39. 39.
    Lachmann RH. Herpes simplex virus-based vectors. Int J Exp Pathol. 2004;85:177–90.PubMedGoogle Scholar
  40. 40.
    Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review, Univ Chicago Press, 2002; S3–S28.Google Scholar
  41. 41.
    Spaete RR, Frenkel N. The herpes simplex virus amplicon: a new eukaryotic defective-virus cloning-amplifying vector. Cell. 1982;30:295–304.PubMedGoogle Scholar
  42. 42.
    Marconi P, Argnani R, Berto E, Epstein AL, Manservigi R. HSV as a vector in vaccine development and gene therapy. Hum Vaccin. 2008;4:91–105.PubMedGoogle Scholar
  43. 43.
    Cuchet D, Potel C, Thomas J, Epstein AL. HSV-1 amplicon vectors: a promising and versatile tool for gene delivery. Expert Opin Biol Ther. 2007;7:975–95.PubMedGoogle Scholar
  44. 44.
    Geller AI, Breakefield XO. A defective HSV-1 vector expresses Escherichia coli beta-galactosidase in cultured peripheral neurons. Science. 1988;241:1667–9.PubMedGoogle Scholar
  45. 45.
    Cunningham C, Davison AJ. A cosmid-based system for constructing mutants of herpes simplex virus type-1. Virology. 1993;197:116–24.PubMedGoogle Scholar
  46. 46.
    Fraefel C, Song S, Lim F, Lang P, Yu L, Wang YM, et al. Helper virus-free transfer of herpes simplex virus type 1 plasmid vectors into neural cells. J Virol. 1996;70:7190–7.PubMedGoogle Scholar
  47. 47.
    Saeki Y, Fraefel C, Ichikawa T, Breakefield XO, Chiocca EA. Improved helper virus-free packaging system for HSV amplicon vectors using an ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome. Mol Ther. 2001;3:591–601.PubMedGoogle Scholar
  48. 48.
    Zaupa C, Revol-Guyot V, Epstein AL. Improved packaging system for generation of high-level noncytotoxic HSV-1 amplicon vectors using Cre-loxP site-specific recombination to delete the packaging signals of defective helper genomes. Hum Gene Ther. 2003;14:1049–63.PubMedGoogle Scholar
  49. 49.
    Sabbioni S, Callegari E, Manservigi M, Argnani R, Corallini A, Negrini M, et al. Use of herpes simplex virus type 1-based amplicon vector for delivery of small interfering RNA. Gene Ther. 2007;14:459–64.PubMedGoogle Scholar
  50. 50.
    Saydam O, Glauser DL, Heid I, Turkeri G, Hilbe M, Jacobs AH, et al. Herpes simplex virus 1 amplicon vector-mediated siRNA targeting epidermal growth factor receptor inhibits growth of human glioma cells in vivo. Mol Ther. 2005;12:803–12.PubMedGoogle Scholar
  51. 51.
    Saydam O, Saydam N, Glauser DL, Pruschy M, Dinh-Van V, Hilbe M, et al. HSV-1 amplicon-mediated post-transcriptional inhibition of Rad51 sensitizes human glioma cells to ionizing radiation. Gene Ther. 2007;14:1143–51.PubMedGoogle Scholar
  52. 52.
    Brockman MA, Knipe DM. Herpes simplex virus vectors elicit durable immune responses in the presence of preexisting host immunity. J Virol. 2002;76:3678–87.PubMedGoogle Scholar
  53. 53.
    Hocknell PK, Wiley RD, Wang XQ, Evans TG, Bowers WJ, Hanke T, et al. Expression of human immunodeficiency virus type 1 gp120 from herpes simplex virus type 1-derived amplicons results in potent, specific, and durable cellular and humoral immune responses. J Virol. 2002;76:5565–80.PubMedGoogle Scholar
  54. 54.
    Lauterbach H, Ried C, Epstein AL, Marconi P, Brocker T. Reduced immune responses after vaccination with a recombinant herpes simplex virus type 1 vector in the presence of antiviral immunity. J Gen Virol. 2005;86:2401–10.PubMedGoogle Scholar
  55. 55.
    Oehmig A, Fraefel C, Breakefield XO, Ackermann M. Herpes simplex virus type 1 amplicons and their hybrid virus partners, EBV, AAV, and retrovirus. Curr Gene Ther. 2004;4:385–408.PubMedGoogle Scholar
  56. 56.
    Kwong AD, Frenkel N. The herpes simplex virus amplicon. IV. Efficient expression of a chimeric chicken ovalbumin gene amplified within defective virus genomes. Virology. 1985;142:421–5.PubMedGoogle Scholar
  57. 57.
    Zhou G, Roizman B. Characterization of a recombinant herpes simplex virus 1 designed to enter cells via the IL13Ralpha2 receptor of malignant glioma cells. J Virol. 2005;79:5272–7.PubMedGoogle Scholar
  58. 58.
    Zhou G, Roizman B. Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL-13alpha2 receptor. Proc Natl Acad Sci USA. 2006;103:5508–13.PubMedGoogle Scholar
  59. 59.
    Zhou G, Ye GJ, Debinski W, Roizman B. Engineered herpes simplex virus 1 is dependent on IL13Ralpha 2 receptor for cell entry and independent of glycoprotein D receptor interaction. Proc Natl Acad Sci USA. 2002;99:15124–9.PubMedGoogle Scholar
  60. 60.
    Wade-Martins R, Smith ER, Tyminski E, Chiocca EA, Saeki Y. An infectious transfer and expression system for genomic DNA loci in human and mouse cells. Nat Biotechnol. 2001;19:1067–70.PubMedGoogle Scholar
  61. 61.
    Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. Structure of Simian Virus-40 at 3.8-Å resolution. Nature. 1991;354:278–84.PubMedGoogle Scholar
  62. 62.
    Nakanishi A, Nakamura A, Liddington R, Kasamatsu H. Identification of amino acid residues within simian virus 40 capsid proteins Vp1, Vp2, and Vp3 that are required for their interaction and for viral infection. J Virol. 2006;80:8891–8.PubMedGoogle Scholar
  63. 63.
    Li PP, Naknanishi A, Tran MA, Ishizu KI, Kawano M, Phillips M, et al. Importance of Vp1 calcium-binding residues in assembly, cell entry, and nuclear entry of simian virus 40. J Virol. 2003;77:7527–38.PubMedGoogle Scholar
  64. 64.
    Kawano M, Inoue T, Tsukamoto H, Takaya T, Enomoto T, Takahashi R, et al. The VP2/VP3 minor capsid protein of simian virus 40 promotes the in vitro assembly of the major capsid protein VP1 into particles. J Biol Chem. 2006;281:10164–73.PubMedGoogle Scholar
  65. 65.
    Colomar MC, Degoumoissahli C, Beard P. Opening and refolding of simian virus 40 and in vitro packaging of foreign DNA. J Virol. 1993;67:2779–86.PubMedGoogle Scholar
  66. 66.
    Botchan M, Topp W, Sambrook J. Arrangement of simian virus 40 sequences in DNA of transformed cells. Cell. 1976;9:269–87.PubMedGoogle Scholar
  67. 67.
    Botchan M, Stringer J, Mitchison T, Sambrook J. Integration and excision of SV40 DNA from the chromosome of a transformed cell. Cell. 1980;20:143–52.PubMedGoogle Scholar
  68. 68.
    Pelkmans L, Kartenbeck J, Helenius A. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol. 2001;3:473–83.PubMedGoogle Scholar
  69. 69.
    Salunke DM, Caspar DLD, Garcea RL. Self-assembly of purified polyomavirus capsid protein VP1. Cell. 1986;46:895–904.PubMedGoogle Scholar
  70. 70.
    Sandalon Z, Dalyot-Herman N, Oppenheim AB, Oppenheim A. In vitro assembly of SV40 virions and pseudovirions: vector development for gene therapy. Hum Gene Ther. 1997;8:843–9.PubMedGoogle Scholar
  71. 71.
    Sandalon Z, Oppenheim A. Self-assembly and protein-protein interactions between the SV40 capsid proteins produced in insect cells. Virology. 1997;237:414–21.PubMedGoogle Scholar
  72. 72.
    Kimchi-Sarfaty C, Arora M, Sandalon Z, Oppenheim A, Gottesman MM. High cloning capacity of in vitro packaged SV40 vectors with no SV40 virus sequences. Hum Gene Ther. 2003;14:167–77.PubMedGoogle Scholar
  73. 73.
    Mukherjee S, Abd-El-Latif M, Bronstein M, Ben-nun-Shaul O, Kler S, Oppenheim A. High cooperativity of the SV40 major capsid protein VP1 in virus assembly. PLoS ONE. 2007;2:e765.PubMedGoogle Scholar
  74. 74.
    Arad U, Zeira E. Abd El-Latif M, Mukherjee S, Mitchell L, Pappo O, et al. Liver-targeted gene therapy by SV40-based vectors using the hydrodynamic injection method. Hum. Gene Ther. 2005;16:361–71.Google Scholar
  75. 75.
    Kondo R, Feitelson MA, Strayer DS. Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent. Gene Ther. 1998;5:575–82.PubMedGoogle Scholar
  76. 76.
    Strayer DS, Agrawal L, Cordelier P, Liu B, Louboutin JP, Marusich E, et al. Long-term gene expression in dividing and nondividing cells using SV40-derived vectors. Mol Biotechnol. 2006;34:257–70.PubMedGoogle Scholar
  77. 77.
    Cordelier P, Morse B, Strayer DS. Targeting CCR5 with siRNAs: using recombinant SV40-derived vectors to protect macrophages and microglia from R5-tropic HIV. Oligonucleotides. 2003;13:281–94.PubMedGoogle Scholar
  78. 78.
    Kimchi-Sarfaty C, Brittain S, Garfield S, Caplen NJ, Tang QQ, Gottesman MM. Efficient delivery of RNA interference effectors via in vitro-packaged SV40 pseudovirions. Hum Gene Ther. 2005;16:1110–5.PubMedGoogle Scholar
  79. 79.
    Kimchi-Sarfaty C, Garfield S, Alexander NS, Ali S, Cruz C, Chinnasamy D, et al. The pathway of uptake of SV40 pseudovirions packaged in vitro: from MHC class I receptors to the nucleus. Gene Ther Mol Biol. 2004;8:439–50.Google Scholar
  80. 80.
    Steinhauer DA, Skehel JJ. Genetics of influenza viruses. Annu Rev Genet. 2002;36:305–32.PubMedGoogle Scholar
  81. 81.
    Ohuchi M, Asaoka N, Sakai T, Ohuchi R. Roles of neuraminidase in the initial stage of influenza virus infection. Microbes Infect. 2006;8:1287–93.PubMedGoogle Scholar
  82. 82.
    Wiley DC, Skehel JJ. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem. 1987;56:365–94.PubMedGoogle Scholar
  83. 83.
    Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem. 2000;69:531–69.PubMedGoogle Scholar
  84. 84.
    Wagner R, Matrosovich M, Klenk HD. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol. 2002;12:159–66.PubMedGoogle Scholar
  85. 85.
    White JM, Hoffman LR, Arevalo JH, Wilson IA. Attachment and entry of influenza virus into host cells. In: Chiu W, Burnett RM, Garcea RL, editors. Structural biology of viruses. New York: Oxford University Press; 1997. p. 80–104.Google Scholar
  86. 86.
    Almeida JD, Edwards DC, Brand CM, Heath TD. Formation of virosomes from influenza subunits and liposomes. Lancet. 1975;2:899–901.PubMedGoogle Scholar
  87. 87.
    de Bruijn IA, Nauta J, Gerez L, Palache AM. Virosomal influenza vaccine: a safe and effective influenza vaccine with high efficacy in elderly and subjects with low pre-vaccination antibody titers. Virus Res. 2004;103:139–45.PubMedGoogle Scholar
  88. 88.
    Huckriede A, Bungener L, Stegmann T, Daemen T, Medema J, Palache AM, et al. The virosome concept for influenza vaccines. Vaccine. 2005;23(Suppl 1):S26–38.PubMedGoogle Scholar
  89. 89.
    Schwaninger R, Waelti E, Zajac P, Wetterwald A, Mueller D, Gimmi CD. Virosomes as new carrier system for cancer vaccines. Cancer Immunol Immunother. 2004;53:1005–17.PubMedGoogle Scholar
  90. 90.
    Waelti E, Wegmann N, Schwaninger R, Wetterwald A, Wingenfeld C, Rothen-Rutishauser B, et al. Targeting her-2/neu with antirat Neu virosomes for cancer therapy. Cancer Res. 2002;62:437–44.PubMedGoogle Scholar
  91. 91.
    Bron R, Ortiz A, Wilschut J. Cellular cytoplasmic delivery of a polypeptide toxin by reconstituted influenza virus envelopes (virosomes). Biochemistry. 1994;33:9110–7.PubMedGoogle Scholar
  92. 92.
    Schoen P, Chonn A, Cullis PR, Wilschut J, Scherrer P. Gene transfer mediated by fusion protein hemagglutinin reconstituted in cationic lipid vesicles. Gene Ther. 1999;6:823–32.PubMedGoogle Scholar
  93. 93.
    de Jonge J, Leenhouts JM, Holtrop M, Schoen P, Scherrer P, Cullis PR, et al. Cellular gene transfer mediated by influenza virosomes with encapsulated plasmid DNA. Biochem J. 2007;405:41–9.PubMedGoogle Scholar
  94. 94.
    de Jonge J, Holtrop M, Wilschut J, Huckriede A. Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs. Gene Ther. 2006;13:400–11.PubMedGoogle Scholar
  95. 95.
    Judge AD, Bola G, Lee AC, MacLachlan I. Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol Ther. 2006;13:494–505.PubMedGoogle Scholar
  96. 96.
    Zalipsky S, Hansen CB, Oaks JM, Allen TM. Evaluation of blood clearance rates and biodistribution of poly(2-oxazoline)-grafted liposomes. J Pharm Sci. 1996;85:133–7.PubMedGoogle Scholar
  97. 97.
    Weissig V, Whiteman KR, Torchilin VP. Accumulation of protein-loaded long-circulating micelles and liposomes in subcutaneous Lewis lung carcinoma in mice. Pharm Res. 1998;15:1552–6.PubMedGoogle Scholar
  98. 98.
    Moghimi SM, Szebeni J. Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res. 2003;42:463–78.PubMedGoogle Scholar
  99. 99.
    Chams V, Bonnafous P, Stegmann T. Influenza hemagglutinin mediated fusion of membranes containing poly(ethylene-glycol) grafted lipids: new insights into the fusion mechanism. FEBS Lett. 1999;448:28–32.PubMedGoogle Scholar
  100. 100.
    Liang W, Levchenko TS, Torchilin VP. Encapsulation of ATP into liposomes by different methods: optimization of the procedure. J Microencapsul. 2004;21:251–61.PubMedGoogle Scholar
  101. 101.
    Steenpass T, Lung A, Schubert R. Tresylated PEG-sterols for coupling of proteins to preformed plain or PEGylated liposomes. Biochim Biophys Acta. 2006;1758:20–8.PubMedGoogle Scholar
  102. 102.
    Mastrobattista E, Schoen P, Wilschut J, Crommelin DJ, Storm G. Targeting influenza virosomes to ovarian carcinoma cells. FEBS Lett. 2001;509:71–6.PubMedGoogle Scholar
  103. 103.
    Khoury M, Louis-Plence P, Escriou V, Noel D, Largeau C, Cantos C, et al. Efficient new cationic liposome formulation for systemic delivery of small interfering RNA silencing tumor necrosis factor alpha in experimental arthritis. Arthritis Rheum. 2006;54:1867–77.PubMedGoogle Scholar
  104. 104.
    Kumar VV, Singh RS, Chaudhuri A. Cationic transfection lipids in gene therapy: successes, set-backs, challenges and promises. Curr Med Chem. 2003;10:1297–306.PubMedGoogle Scholar
  105. 105.
    Ewert K, Slack NL, Ahmad A, Evans HM, Lin AJ, Samuel CE, et al. Cationic lipid-DNA complexes for gene therapy: understanding the relationship between complex structure and gene delivery pathways at the molecular level. Curr Med Chem. 2004;11:133–49.PubMedGoogle Scholar
  106. 106.
    Karmali PP, Chaudhuri A. Cationic liposomes as non-viral carriers of gene medicines: resolved issues, open questions, and future promises. Med Res Rev. 2007;27:696–722.PubMedGoogle Scholar
  107. 107.
    Ochiai H, Kurokawa M, Matsui S, Yamamoto T, Kuroki Y, Kishimoto C, et al. Infection enhancement of influenza A NWS virus in primary murine macrophages by anti-hemagglutinin monoclonal antibody. J Med Virol. 1992;36:217–21.PubMedGoogle Scholar
  108. 108.
    Tamura M, Webster RG, Ennis FA. Subtype cross-reactive, infection-enhancing antibody responses to influenza A viruses. J Virol. 1994;68:3499–504.PubMedGoogle Scholar
  109. 109.
    Cusi MG, Terrosi C, Savellini GG, Di Genova G, Zurbriggen R, Correale P. Efficient delivery of DNA to dendritic cells mediated by influenza virosomes. Vaccine. 2004;22:735–9.PubMedGoogle Scholar
  110. 110.
    Zhu X, Meng G, Dickinson BL, Li X, Mizoguchi E, Miao L, et al. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. J Immunol. 2001;166:3266–76.PubMedGoogle Scholar
  111. 111.
    Kuroya M, Ishida N. Newborn virus pneumonitis (type Sendai). II. The isolation of a new virus possessing hemagglutinin activity. Yokohama Med Bull. 1953;4:217–33.PubMedGoogle Scholar
  112. 112.
    Okada Y. Sendai virus-induced cell-fusion. Methods Enzymol. 1993;221:18–41.PubMedGoogle Scholar
  113. 113.
    Kaneda Y. Applications of hemagglutinating virus of Japan in therapeutic delivery systems. Expert Opin Drug Deliv. 2008;5:221–33.PubMedGoogle Scholar
  114. 114.
    Bagai S, Puri A, Blumenthal R, Sarkar DP. Hemagglutinin-neuraminidase enhances F protein-mediated membrane fusion of reconstituted Sendai virus envelopes with cells. J Virol. 1993;67:3312–8.PubMedGoogle Scholar
  115. 115.
    Bagai S, Sarkar DP. Targeted delivery of hygromycin B using reconstituted Sendai viral envelopes lacking hemagglutinin-neuraminidase. FEBS Lett. 1993;326:183–8.PubMedGoogle Scholar
  116. 116.
    Ramani K, Bora RS, Kumar M, Tyagi SK, Sarkar DP. Novel gene delivery to liver cells using engineered virosomes. FEBS Lett. 1997;404:164–8.PubMedGoogle Scholar
  117. 117.
    Kaneda Y, Iwai K, Uchida T. Increased expression of DNA cointroduced with nuclear protein in adult rat liver. Science. 1989;243:375–8.PubMedGoogle Scholar
  118. 118.
    Kato K, Nakanishi M, Kaneda Y, Uchida T. Okada Y. Expression of hepatitis B virus surface antigen in adult rat liver. Co-introduction of DNA and nuclear protein by a simplified liposome method. J Biol Chem. 1991;266:3361–4.Google Scholar
  119. 119.
    Dzau VJ, Mann MJ, Morishita R, Kaneda Y. Fusigenic viral liposome for gene therapy in cardiovascular diseases. Proc Natl Acad Sci USA. 1996;93:11421–5.PubMedGoogle Scholar
  120. 120.
    Nakamura N, Hart DA, Frank CB, Marchuk LL, Shrive NG, Ota N, et al. Efficient transfer of intact oligonucleotides into the nucleus of ligament scar fibroblasts by HVJ-cationic liposomes is correlated with effective antisense gene inhibition. J Biochem (Tokyo). 2001;129:755–9.Google Scholar
  121. 121.
    Kaneda Y, Nakajima T, Nishikawa T, Yamamoto S, Ikegami H, Suzuki N, et al. Hemagglutinating virus of Japan (HVJ) envelope vector as a versatile gene delivery system. Mol Ther. 2002;6:219–26.PubMedGoogle Scholar
  122. 122.
    Kaneda Y, Yamamoto S, Nakajima T. Development of HVJ envelope vector and its application to gene therapy. Adv Genet. 2005;53:307–32.PubMedGoogle Scholar
  123. 123.
    Nakanishi M, Uchida T, Kim J, Okada Y. Glycoproteins of Sendai virus (HVJ) have a critical ratio for fusion between virus envelopes and cell membranes. Exp Cell Res. 1982;142:95–101.PubMedGoogle Scholar
  124. 124.
    Zhang QX, Li Y, Shi YH, Zhang YL. HVJ envelope vector, a versatile delivery system: Its development, application, and perspectives. Biochem Biophys Res Commun. 2008;373:345–9.PubMedGoogle Scholar
  125. 125.
    GenomONE-Neo HVJ Envelope Transfection Kit : Cosmo Bio Co., Ltd. (accessed 7/19/09).
  126. 126.
    Mima H, Tomoshige R, Kanamori T, Tabata Y, Yamamoto S, Ito S, et al. Biocompatible polymer enhances the in vitro and in vivo transfection efficiency of HVJ envelope vector. J Gene Med. 2005;7:888–97.PubMedGoogle Scholar
  127. 127.
    Mima H, Yamamoto S, Ito M, Tomoshige R, Tabata Y, Tamai K, et al. Targeted chemotherapy against intraperitoneally disseminated colon carcinoma using a cationized gelatin-conjugated HVJ envelope vector. Mol Cancer Ther. 2006;5:1021–8.PubMedGoogle Scholar
  128. 128.
    Kawachi M, Tamai K, Saga K, Yamazaki T, Fujita H, Shimbo T, et al. Development of tissue-targeting hemagglutinating virus of Japan envelope vector for successful delivery of therapeutic gene to mouse skin. Hum Gene Ther. 2007;18:881–94.PubMedGoogle Scholar
  129. 129.
    Ito M, Yamamoto S, Nimura K, Hiraoka K, Tamai K, Kaneda Y. Rad51 siRNA delivered by HVJ envelope vector enhances the anti-cancer effect of cisplatin. J Gene Med. 2005;7:1044–52.PubMedGoogle Scholar
  130. 130.
    Watanabe A, Arai M, Yamazaki M, Koitabashi N, Wuytack F, Kurabayashi M. Phospholamban ablation by RNA interference increases Ca2+ uptake into rat cardiac myocyte sarcoplasmic reticulum. J Mol Cell Cardiol. 2004;37:691–8.PubMedGoogle Scholar
  131. 131.
    Minamisawa S, Hoshijima M, Chu GX, Ward CA, Frank K, Gu YS, et al. Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell. 1999;99:313–22.PubMedGoogle Scholar
  132. 132.
    Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J Mol Biol. 2005;348:1079–90.PubMedGoogle Scholar
  133. 133.
    Kurooka M, Kaneda Y. Inactivated Sendai virus particles eradicate tumors by inducing immune responses through blocking regulatory T cells. Cancer Res. 2007;67:227–36.PubMedGoogle Scholar
  134. 134.
    Fujihara A, Kurooka M, Miki T, Kaneda Y. Intratumoral injection of inactivated Sendai virus particles elicits strong antitumor activity by enhancing local CXCL10 expression and systemic NK cell activation. Cancer Immunol Immunother. 2008;57:73–84.PubMedGoogle Scholar

Copyright information

© US Government 2009

Authors and Affiliations

  • Paul E. Lund
    • 1
  • Ryan C. Hunt
    • 2
  • Michael M. Gottesman
    • 1
  • Chava Kimchi-Sarfaty
    • 2
  1. 1.Laboratory of Cell Biology, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Center for Biologics Evaluation and ResearchFood and Drug AdministrationBethesdaUSA

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