About this Journal Submit a Manuscript Table of Contents
Journal of Drug Delivery
Volume 2011 (2011), Article ID 296151, 12 pages
http://dx.doi.org/10.1155/2011/296151
Review Article

The Trojan Horse Liposome Technology for Nonviral Gene Transfer across the Blood-Brain Barrier

1Department of Medicine, UCLA, Warren Hall 13-164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
2ArmaGen Technologies, Inc., Santa Monica, CA 90401, USA

Received 5 July 2011; Revised 4 September 2011; Accepted 4 September 2011

Academic Editor: Abdelwahab Omri

Copyright © 2011 Ruben J. Boado and William M. Pardridge. 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.

Linked References

  1. W. M. Pardridge, “Drug and gene delivery to the brain: the vascular route,” Neuron, vol. 36, no. 4, pp. 555–558, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. K. W. Mok, A. M. Lam, and P. R. Cullis, “Stabilized plasmid-lipid particles: factors influencing plasmid entrapment and transfection properties,” Biochimica et Biophysica Acta, vol. 1419, no. 2, pp. 137–150, 1999. View at Publisher · View at Google Scholar · View at Scopus
  3. N. Shi and W. M. Pardridge, “Noninvasive gene targeting to the brain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 13, pp. 7567–7572, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. R. J. Boado, “Blood-brain barrier transport of non-viral gene and RNAi therapeutics,” Pharmaceutical Research, vol. 24, no. 9, pp. 1772–1787, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. A. P. Byrnes, J. E. Rusby, M. J. Wood, and H. M. Charlton, “Adenovirus gene transfer causes inflammation in the brain,” Neuroscience, vol. 66, no. 4, pp. 1015–1024, 1995. View at Publisher · View at Google Scholar · View at Scopus
  6. M. J. Wood, H. M. Charlton, K. J. Wood, K. Kajiwara, and A. P. Byrnes, “Immune responses to adenovirus vectors in the nervous system,” Trends in Neurosciences, vol. 19, no. 11, pp. 497–501, 1996. View at Publisher · View at Google Scholar · View at Scopus
  7. J. G. Smith, S. E. Raper, E. B. Wheeldon et al., “Intracranial administration of adenovirus expressing HSV-TK in combination with ganciclovir produces a dose-dependent, self-limiting inflammatory response,” Human Gene Therapy, vol. 8, no. 8, pp. 943–954, 1997. View at Scopus
  8. M. J. Driesse, A. J. Vincent, P. A. Sillevis Smitt et al., “Intracerebral injection of adenovirus harboring the HSVtk gene combined with ganciclovir administration: toxicity study in nonhuman primates,” Gene Therapy, vol. 5, no. 8, pp. 1122–1129, 1998. View at Scopus
  9. M. J. Driesse, M. C. Esandi, J. M. Kros et al., “Intra-CSF administered recombinant adenovirus causes an immune response-mediated toxicity,” Gene Therapy, vol. 7, no. 16, pp. 1401–1409, 2000. View at Scopus
  10. U. Herrlinger, C. M. Kramm, K. S. Aboody-Guterman et al., “Pre-existing herpes simplex virus 1 (HSV-1) immunity decreases, but does not abolish, gene transfer to experimental brain tumors by a HSV-1 vector,” Gene Therapy, vol. 5, no. 6, pp. 809–819, 1998. View at Scopus
  11. M. M. McMenamin, A. P. Byrnes, H. M. Charlton, R. S. Coffin, D. S. Latchman, and M. J. Wood, “A γ34.5 mutant of herpes simplex 1 causes severe inflammation in the brain,” Neuroscience, vol. 83, no. 4, pp. 1225–1237, 1998. View at Publisher · View at Google Scholar · View at Scopus
  12. R. A. Dewey, G. Morrissey, C. M. Cowsill et al., “Chronic brain inflammation and persistent herpes simplex virus 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: implications for clinical trials,” Nature Medicine, vol. 5, no. 11, pp. 1256–1263, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. M. S. Lawrence, H. G. Foellmer, J. D. Elsworth et al., “Inflammatory responses and their impact on β-galactosidase transgene expression following adenovirus vector delivery to the primate caudate nucleus,” Gene Therapy, vol. 6, no. 8, pp. 1368–1379, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. Y. Stallwood, K. D. Fisher, P. H. Gallimore, and V. Mautner, “Neutralisation of adenovirus infectivity by ascitic fluid from ovarian cancer patients,” Gene Therapy, vol. 7, no. 8, pp. 637–643, 2000. View at Scopus
  15. K. Kajiwara, A. P. Byrnes, Y. Ohmoto, H. M. Charlton, M. J. Wood, and K. J. Wood, “Humoral immune responses to adenovirus vectors in the brain,” Journal of Neuroimmunology, vol. 103, no. 1, pp. 8–15, 2000. View at Publisher · View at Google Scholar · View at Scopus
  16. H. Matsui, L. G. Johnson, S. H. Randell, and R. C. Boucher, “Loss of binding and entry of liposome-DNA complexes decreases transfection efficiency in differentiated airway epithelial cells,” Journal of Biological Chemistry, vol. 272, no. 2, pp. 1117–1126, 1997. View at Publisher · View at Google Scholar · View at Scopus
  17. L. G. Barron, L. S. Uyechi, and F. C. Szoka Jr., “Cationic lipids are essential for gene delivery mediated by intravenous administration of lipoplexes,” Gene Therapy, vol. 6, no. 6, pp. 1179–1183, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. G. Osaka, K. Carey, A. Cuthbertson et al., “Pharmacokinetics, tissue distribution, and expression Efficiency of plasmid [33P]DNA following intravenous administration of DNA/cationic lipid complexes in mice: use of a novel radionuclide approach,” Journal of Pharmaceutical Sciences, vol. 85, no. 6, pp. 612–618, 1996. View at Scopus
  19. W. M. Pardridge, “Gene targeting in vivo with pegylated immunoliposomes,” Methods in Enzymology, vol. 373, pp. 507–528, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. N. Shi, R. J. Boado, and W. M. Pardridge, “Receptor-mediated gene targeting to tissues in vivo following intravenous administration of pegylated immunoliposomes,” Pharmaceutical Research, vol. 18, no. 8, pp. 1091–1095, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. N. Shi, Y. Zhang, C. Zhu, R. J. Boado, and W. M. Pardridge, “Brain-specific expression of an exogenous gene after i.v. administration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 22, pp. 12754–12759, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. Y. Zhang, F. Calon, C. Zhu, R. J. Boado, and W. M. Pardridge, “Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism,” Human Gene Therapy, vol. 14, no. 1, pp. 1–12, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. Y. Zhang, Y. F. Zhang, J. Bryant, A. Charles, R. J. Boado, and W. M. Pardridge, “Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer,” Clinical Cancer Research, vol. 10, no. 11, pp. 3667–3677, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. D. Papahadjopoulos, T. M. Allen, A. Gabizon et al., “Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 24, pp. 11460–11464, 1991. View at Scopus
  25. A. Gabizon and D. Papahadjopoulos, “Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 18, pp. 6949–6953, 1988. View at Scopus
  26. R. J. Boado, Y. F. Zhang, Y. Zhang, and W. M. Pardridge, “Humanization of anti-human insulin receptor antibody for drug targeting across the human blood-brain barrier,” Biotechnology and Bioengineering, vol. 96, no. 2, pp. 381–391, 2007. View at Publisher · View at Google Scholar · View at PubMed
  27. F. Schlachetzki, Y. Zhang, R. J. Boado, and W. M. Pardridge, “Gene therapy of the brain: the trans-vascular approach,” Neurology, vol. 62, no. 8, pp. 1275–1281, 2004.
  28. Y. Zhang, R. J. Boado, and W. M. Pardridge, “Marked enhancement in gene expression by targeting the human insulin receptor,” Journal of Gene Medicine, vol. 5, no. 2, pp. 157–163, 2003. View at Publisher · View at Google Scholar · View at PubMed
  29. Y. Zhang, R. J. Boado, and W. M. Pardridge, “In vivo knockdown of gene expression in brain cancer with intravenous RNAi in adult rats,” Journal of Gene Medicine, vol. 5, no. 12, pp. 1039–1045, 2003. View at Publisher · View at Google Scholar · View at PubMed
  30. Y. Zhang, F. Schlachetzki, Y. F. Zhang, R. J. Boado, and W. M. Pardridge, “Normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism with intravenous nonviral gene therapy and a brain-specific promoter,” Human Gene Therapy, vol. 15, no. 4, pp. 339–350, 2004. View at Publisher · View at Google Scholar · View at PubMed
  31. Y. Zhang, H. Y. Lee, R. J. Boado, and W. M. Pardridge, “Receptor-mediated delivery of an antisense gene to human brain cancer cells,” Journal of Gene Medicine, vol. 4, no. 2, pp. 183–194, 2002. View at Publisher · View at Google Scholar · View at PubMed
  32. C. F. Xia, Y. Zhang, Y. Zhang, R. J. Boado, and W. M. Pardridge, “Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology,” Pharmaceutical Research, vol. 24, no. 12, pp. 2309–2316, 2007. View at Publisher · View at Google Scholar · View at PubMed
  33. C. Chu, Y. Zhang, R. J. Boado, and W. M. Pardridge, “Decline in exogenous gene expression in primate brain following intravenous administration is due to plasmid degradation,” Pharmaceutical Research, vol. 23, no. 7, pp. 1586–1590, 2006. View at Publisher · View at Google Scholar · View at PubMed
  34. Y. Zhang, F. Schlachetzki, and W. M. Pardridge, “Global non-viral gene transfer to the promate brain following intravenous administration,” Molecular Therapy, vol. 7, no. 1, pp. 11–17, 2003. View at Publisher · View at Google Scholar
  35. Y. Zhang, F. Schlachetzki, J. Y. Li, R. J. Boado, and W. M. Pardridge, “Organ-specific gene expression in the rhesus monkey eye following intravenous non-viral gene transfer,” Molecular Vision, vol. 9, pp. 465–472, 2003. View at Scopus
  36. Y. Zhang, Y. Wang, R. J. Boado, and W. M. Pardridge, “Lysosomal enzyme replacement of the brain with intravenous non-viral gene transfer,” Pharmaceutical Research, vol. 25, no. 2, pp. 400–406, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. Y. A. Ioannou, “Gene therapy for lysosomal storage disorders with neuropathology,” Journal of the American Society of Nephrology, vol. 11, no. 8, pp. 1542–1547, 2000. View at Scopus
  38. W. C. Aird, “Phenotypic heterogeneity of the endothelium I. Structure, function, and mechanisms,” Circulation Research, vol. 100, no. 2, pp. 158–173, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. A. Bosch, E. Perret, N. Desmaris, D. Trono, and J. M. Heard, “Reversal of pathology in the entire brain of mucopolysaccharidosis type VII mice after lentivirus-mediated gene transfer,” Human Gene Therapy, vol. 11, no. 8, pp. 1139–1150, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. M. M. Mouradian and T. N. Chase, “Gene therapy for Parkinson's disease: an approach to the prevention or palliation of levodopa-associated motor complications,” Experimental Neurology, vol. 144, no. 1, pp. 51–57, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. R. Mandil, E. Ashkenazi, M. Blass et al., “Protein kinase Cα and protein kinase Cδ play opposite roles in the proliferation and apoptosis of glioma cells,” Cancer Research, vol. 61, no. 11, pp. 4612–4619, 2001. View at Scopus
  42. I. Nagatsu, H. Ichinose, M. Sakai, K. Titani, M. Suzuki, and T. Nagatsu, “Immunocytochemical localization of GTP cyclohydrolase I in the brain, adrenal gland, and liver of mice,” Journal of Neural Transmission, vol. 102, no. 3, pp. 175–188, 1995. View at Publisher · View at Google Scholar · View at Scopus
  43. O. Hwang, H. Baker, S. Gross, and T. H. Joh, “Localization of GTP cyclohydrolase in monoaminergic but not nitric oxide-producing cells,” Synapse, vol. 28, no. 2, pp. 140–153, 1998. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Shimoji, K. Hirayama, K. Hyland, and G. Kapatos, “GTP cyclohydrolase I gene expression in the brains of male and female hph-1 mice,” Journal of Neurochemistry, vol. 72, no. 2, pp. 757–764, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. I. Nagatsu, R. Arai, M. Sakai et al., “Immunohistochemical colocalization of GTP cyclohydrolase I in the nigrostriatal system with tyrosine hydroxylase,” Neuroscience Letters, vol. 224, no. 3, pp. 185–188, 1997. View at Publisher · View at Google Scholar · View at Scopus
  46. N. Kaneda, T. Sasaoka, K. Kobayashi et al., “Tissue-specific and high-level expression of the human tyrosine hydroxylase gene in transgenic mice,” Neuron, vol. 6, no. 4, pp. 583–594, 1991. View at Publisher · View at Google Scholar · View at Scopus
  47. N. Min, T. H. Joh, K. S. Kim, C. Peng, and J. H. Son, “5' Upstream DNA sequence of the rat tyrosine hydroxylase gene directs high-level and tissue-specific expression to catecholaminergic neurons in the central nervous system of transgenic mice,” Molecular Brain Research, vol. 27, no. 2, pp. 281–289, 1994. View at Publisher · View at Google Scholar · View at Scopus
  48. C. F. Xia, C. Chu, J. Li et al., “Comparison of cDNA and genomic forms of tyrosine hydroxylase gene therapy of the brain with Trojan horse liposomes,” Journal of Gene Medicine, vol. 9, no. 7, pp. 605–612, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. Y. F. Zhang, R. J. Boado, and W. M. Pardridge, “Absence of toxicity of chronic weekly intravenous gene therapy with pegylated immunoliposomes,” Pharmaceutical Research, vol. 20, no. 11, pp. 1779–1785, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. T. Skjørringe, T. Gjetting, and T. G. Jensen, “A modified protocol for efficient DNA encapsulation into pegylated immunoliposomes (PILs),” Journal of Controlled Release, vol. 139, no. 2, pp. 140–145, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. Y. T. Ko, R. Bhattacharya, and U. Bickel, “Liposome encapsulated polyethylenimine/ODN polyplexes for brain targeting,” Journal of Controlled Release, vol. 133, no. 3, pp. 230–237, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. A. Schnyder, S. Krähenbühl, J. Drewe, and J. Huwyler, “Targeting of daunomycin using biotinylated immunoliposomes: pharmacokinetics, tissue distribution and in vitro pharmacological effects,” Journal of Drug Targeting, vol. 13, no. 5, pp. 325–335, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. W. M. Pardridge, J. L. Buciak, and P. M. Friden, “Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo,” Journal of Pharmacology and Experimental Therapeutics, vol. 259, no. 1, pp. 66–70, 1991. View at Scopus
  54. J. H. Lee, B. Engelhardt, J. Lesley, U. Bickel, and W. M. Pardridge, “Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse,” Journal of Pharmacology and Experimental Therapeutics, vol. 292, no. 3, pp. 1048–1052, 2000. View at Scopus
  55. R. J. Boado, Y. Zhang, Y. Wang, and W. M. Pardridge, “Engineering and expression of a chimeric transferrin receptor monoclonal antibody for blood-brain barrier delivery in the mouse,” Biotechnology and Bioengineering, vol. 102, no. 4, pp. 1251–1258, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. B. Gupta, T. S. Levchenko, and V. P. Torchilin, “TAT peptide-modified liposomes provide enhanced gene delivery to intracranial human brain tumor xenografts in nude mice,” Oncology Research, vol. 16, no. 8, pp. 351–359, 2007. View at Scopus
  57. V. P. Chekhonin, Y. A. Zhirkov, O. I. Gurina et al., “PEGylated immunoliposomes directed against brain astrocytes,” Drug Delivery, vol. 12, no. 1, pp. 1–6, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Kawakami, F. Yamashita, K. Nishida, J. Nakamura, and M. Hashida, “Glycosylated cationic liposomes for cell-selective gene delivery,” Critical Reviews in Therapeutic Drug Carrier Systems, vol. 19, no. 2, pp. 171–190, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. T. Montier, P. Delépine, T. Benvegnu et al., “Efficient gene transfer into human epithelial cell lines using glycosylated cationic carriers and neutral glycosylated co-lipids,” Blood Cells, Molecules, and Diseases, vol. 32, no. 2, pp. 271–282, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. W. M. Pardridge, Y. S. Kang, J. L. Buciak, and J. Yang, “Human insulin receptor monoclonal antibody undergoes high affinity binding to human brain capillaries in vitro and rapid transcytosis through the blood-brain barrier in vivo in the primate,” Pharmaceutical Research, vol. 12, no. 6, pp. 807–816, 1995. View at Scopus