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Delivery of Viral Vectors to Tumor Cells: Extracellular Transport, Systemic Distribution, and Strategies for Improvement

  • Nanobioengineering
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It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tissues. In general, gene delivery is hindered by various physiological barriers to virus transport from the site of injection to the nucleus of tumor cells and is limited by normal tissue tolerance of toxicity determined by local concentrations of transgene products and viral proteins. To illustrate the obstacles encountered in the delivery and yet limit the scope of discussion, this review focuses only on extracellular transport in solid tumors and distribution of viral vectors in normal organs after they are injected intravenously or intratumorally. This review also discusses current strategies for improving intratumoral transport and specificity of viral vectors.

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REFERENCES

  1. Abdul-Ghani, R., P. Ohana, I. Matouk, S. Ayesh, B. Ayesh, M. Laster, O. Bibi, H. Giladi, K. Molnar-Kimber, M. A. Sughayer, N. de Groot, and A. Hochberg. Use of transcriptional regulatory sequences of telomerase (hTER and hTERT) for selective killing of cancer cells. Mol. Ther. 2:539–544, 2000.

    Article  PubMed  CAS  Google Scholar 

  2. Acker, T., and K. H. Plate. A role for hypoxia and hypoxia-inducible transcription factors in tumor physiology. J. Mol. Med. 80:562–575, 2002.

    Article  PubMed  CAS  Google Scholar 

  3. Alemany, R., C. Balague, and D. T. Curiel. Replicative adenoviruses for cancer therapy. Nat. Biotechnol. 18:723–727, 2000.

    Article  PubMed  CAS  Google Scholar 

  4. Alemany, R., and D. T. Curiel. CAR-binding ablation does not change biodistribution and toxicity of adenoviral vectors. Gene Ther. 8:1347–1353, 2001.

    Article  PubMed  CAS  Google Scholar 

  5. Alemany, R., K. Suzuki, and D. T. Curiel. Blood clearance rates of adenovirus type 5 in mice. J. Gen. Virol. 81:2605–2609, 2000.

    PubMed  CAS  Google Scholar 

  6. Anderson, W. F., R. M. Blaese, and K. Culver. The ADA human gene therapy clinical protocol: Points to consider response with clinical protocol, July 6, 1990. Hum. Gene Ther. 1:331–362, 1990.

    PubMed  Google Scholar 

  7. Baranowski, E., C. M. Ruiz-Jarabo, and E. Domingo. Evolution of cell recognition by viruses. Science 292:1102–1105, 2001.

    Article  PubMed  CAS  Google Scholar 

  8. Bartlett, J. S., J. Kleinschmidt, R. C. Boucher, and R. J. Samulski. Targeted adeno-associated virus vector transduction of nonpermissive cells mediated by a bispecific F(ab’gamma)2 antibody. Nat. Biotechnol. 17:181–186, 1999.

    Article  PubMed  CAS  Google Scholar 

  9. Benedict, C. A., R. Y. Tun, D. B. Rubinstein, T. Guillaume, P. M. Cannon, and W. F. Anderson. Targeting retroviral vectors to CD34-expressing cells: Binding to CD34 does not catalyze virus-cell fusion. Hum. Gene Ther. 10:545–557, 1999.

    Article  PubMed  CAS  Google Scholar 

  10. Bergelson, J. M., J. A. Cunningham, G. Droguett, E. A. Kurt-Jones, A. Krithivas, J. S. Hong, M. S. Horwitz, R. L. Crowell, and R. W. Finberg. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275:1320–1323, 1997.

    Article  PubMed  CAS  Google Scholar 

  11. Blackburn, R. V., S. S. Galoforo, P. M. Corry, and Y. J. Lee. Adenoviral-mediated transfer of a heat-inducible double suicide gene into prostate carcinoma cells. Cancer Res. 58:1358–1362, 1998.

    PubMed  CAS  Google Scholar 

  12. Blancher, C., and A. L. Harris. The molecular basis of the hypoxia response pathway: Tumour hypoxia as a therapy target. Cancer Metastasis Rev. 17:187–194, 1998.

    Article  PubMed  CAS  Google Scholar 

  13. Bobo, R. H., D. W. Laske, A. Akbasak, P. F. Morrison, R. L. Dedrick, and E. H. Oldfield. Convection-enhanced delivery of macromolecules in the brain. Proc. Natl. Acad. Sci. USA 91:2076–2080, 1994.

    PubMed  CAS  Google Scholar 

  14. Bonnet, M. C., J. Tartaglia, F. Verdier, P. Kourilsky, A. Lindberg, M. Klein, and P. Moingeon. Recombinant viruses as a tool for therapeutic vaccination against human cancers. Immunol. Lett. 74:11–25, 2000.

    Article  PubMed  CAS  Google Scholar 

  15. Boucher, Y., L. T. Baxter, and R. K. Jain. Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: Implications for therapy. Cancer Res. 50:4478–4484, 1990.

    PubMed  CAS  Google Scholar 

  16. Boucher, Y., and R. K. Jain. Microvascular pressure is the principal driving force for interstitial hypertension in solid tumors: Implications for vascular collapse. Cancer Res. 52:5110–5114, 1992.

    PubMed  CAS  Google Scholar 

  17. Bowers, W. J., J. A. Olschowka, and H. J. Federoff. Immune responses to replication-defective HSV-1 type vectors within the CNS: Implications for gene therapy. Gene Ther. 10:941–945, 2003.

    Article  PubMed  CAS  Google Scholar 

  18. Bramson, J. L., M. Hitt, J. Gauldie, and F. L. Graham. Pre-existing immunity to adenovirus does not prevent tumor regression following intratumoral administration of a vector expressing IL-12 but inhibits virus dissemination. Gene Ther. 4:1069–1076, 1997.

    Article  PubMed  CAS  Google Scholar 

  19. Brizel, D. M., T. Schroeder, R. L. Scher, S. Walenta, R. W. Clough, M. W. Dewhirst, and W. Mueller-Klieser. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 51:349–353, 2001.

    Article  PubMed  CAS  Google Scholar 

  20. Brown, B. D., and D. Lillicrap. Dangerous liaisons: The role of “danger” signals in the immune response to gene therapy. Blood 100:1133–1140, 2002.

    Article  PubMed  CAS  Google Scholar 

  21. Casper, E. S., G. K. Schwartz, A. Sugarman, D. Leung, and M. F. Brennan. Phase I trial of dose-intense liposome-encapsulated doxorubicin in patients with advanced sarcoma. J. Clin. Oncol. 15:2111–2117, 1997.

    PubMed  CAS  Google Scholar 

  22. Chada, S., R. Ramesh, and A. M. Mhashilkar. Cytokine- and chemokine-based gene therapy for cancer. Curr. Opin. Mol. Ther. 5:463–474, 2003.

    PubMed  CAS  Google Scholar 

  23. Chen, D., B. Murphy, R. Sung, and J. S. Bromberg. Adaptive and innate immune responses to gene transfer vectors: Role of cytokines and chemokines in vector function. Gene Ther. 10:991–998, 2003.

    Article  PubMed  CAS  Google Scholar 

  24. Chen, M. Y., R. R. Lonser, P. F. Morrison, L. S. Governale, and E. H. Oldfield. Variables affecting convection-enhanced delivery to the striatum: A systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time. J. Neurosurg. 90:315–320, 1999.

    PubMed  CAS  Google Scholar 

  25. Christiansen, J., and A. K. Rajasekaran. Biological impediments to monoclonal antibody-based cancer immunotherapy. Mol. Cancer Ther. 3:1493–501, 2004.

    PubMed  CAS  Google Scholar 

  26. Chung, I., P. E. Schwartz, R. G. Crystal, G. Pizzorno, J. Leavitt, and A. B. Deisseroth. Use of l-plastin promoter to develop an adenoviral system that confers transgene expression in ovarian cancer cells but not in normal mesothelial cells. Cancer Gene Ther. 6:99–106, 1999.

    Article  PubMed  CAS  Google Scholar 

  27. Cichon, G., H. H. Schmidt, T. Benhidjeb, P. Loser, S. Ziemer, R. Haas, N. Grewe, F. Schnieders, J. Heeren, M. P. Manns, P. M. Schlag, and M. Strauss. Intravenous administration of recombinant adenoviruses causes thrombocytopenia, anemia and erythroblastosis in rabbits. J. Gene Med. 1:360–371, 1999.

    Article  PubMed  CAS  Google Scholar 

  28. Cornetta, K., R. C. Moen, K. Culver, R. A. Morgan, J. R. McLachlin, S. Sturm, J. Selegue, W. London, R. M. Blaese, and W. F. Anderson. Amphotropic murine leukemia retrovirus is not an acute pathogen for primates. Hum. Gene Ther. 1:15–30, 1990.

    PubMed  CAS  Google Scholar 

  29. Croyle, M. A., S. M. Callahan, A. Auricchio, G. Schumer, K. D. Linse, J. M. Wilson, L. J. Brunner, and G. P. Kobinger. PEGylation of a vesicular stomatitis virus G pseudotyped lentivirus vector prevents inactivation in serum. J. Virol. 78:912–921, 2004.

    Article  PubMed  CAS  Google Scholar 

  30. Croyle, M. A., N. Chirmule, Y. Zhang, and J. M. Wilson. “Stealth” adenoviruses blunt cell-mediated and humoral immune responses against the virus and allow for significant gene expression upon readministration in the lung. J. Virol. 75:4792–4801, 2001.

    Article  PubMed  CAS  Google Scholar 

  31. Croyle, M. A., N. Chirmule, Y. Zhang, and J. M. Wilson. PEGylation of E1-deleted adenovirus vectors allows significant gene expression on readministration to liver. Hum. Gene Ther. 13:1887–1900, 2002.

    Article  PubMed  CAS  Google Scholar 

  32. Crystal, R. G. Transfer of genes to humans: Early lessons and obstacles to success. Science 270:404–410, 1995.

    PubMed  CAS  Google Scholar 

  33. Curiel, D. T. Gene therapy for carcinoma of the breast: Genetic ablation strategies. Breast Cancer Res. 2:45–49, 2000.

    Article  PubMed  CAS  Google Scholar 

  34. Davidson, B. L., J. M. Hilfinger, and S. J. Beer. Extended release of adenovirus from polymer microspheres: Potential use in gene therapy for brain tumors. Adv. Drug Deliv. Rev. 27:59–66, 1997.

    Article  PubMed  Google Scholar 

  35. DePolo, N. J., C. E. Harkleroad, M. Bodner, A. T. Watt, C. G. Anderson, J. S. Greengard, K. K. Murthy, T. W. Dubensky Jr., and D. J. Jolly. The resistance of retroviral vectors produced from human cells to serum inactivation in vivo and in vitro is primate species dependent. J. Virol. 73:6708–6714, 1999.

    PubMed  CAS  Google Scholar 

  36. DeWeese, T. L., H. van der Poel, S. Li, B. Mikhak, R. Drew, M. Goemann, U. Hamper, R. DeJong, N. Detorie, R. Rodriguez, T. Haulk, A. M. DeMarzo, S. Piantadosi, D. C. Yu, Y. Chen, D. R. Henderson, M. A. Carducci, W. G. Nelson, and J. W. Simons. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res. 61:7464–7472, 2001.

    PubMed  CAS  Google Scholar 

  37. Dewhirst, M. W. Concepts of oxygen transport at the microcirculatory level. Semin. Rad. Oncol. 8:143–150, 1998.

    CAS  Google Scholar 

  38. Dmitriev, I., V. Krasnykh, C. R. Miller, M. Wang, E. Kashentseva, G. Mikheeva, N. Belousova, and D. T. Curiel. An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J. Virol. 72:9706–9713, 1998.

    PubMed  CAS  Google Scholar 

  39. Douglas, J. T., B. E. Rogers, M. E. Rosenfeld, S. I. Michael, M. Feng, and D. T. Curiel. Targeted gene delivery by tropism-modified adenoviral vectors. Nat. Biotechnol. 14:1574–1578, 1996.

    Article  PubMed  CAS  Google Scholar 

  40. Edelstein, M. L., M. R. Abedi, J. Wixon, and R. M. Edelstein. Gene therapy clinical trials worldwide 1989—2004—An overview. J. Gene Med. 6:597–602, 2004.

    Article  PubMed  Google Scholar 

  41. Endler, E. E., K. A. Duca, P. F. Nealey, G. M. Whitesides, and J. Yin. Propagation of viruses on micropatterned host cells. Biotechnol. Bioeng. 81:719–725, 2003.

    Article  PubMed  CAS  Google Scholar 

  42. Etienne-Julan, M., P. Roux, S. Carillo, P. Jeanteur, and M. Piechaczyk. The efficiency of cell targeting by recombinant retroviruses depends on the nature of the receptor and the composition of the artificial cell-virus linker. J. Gen. Virol. 73(Pt 12):3251–3255, 1992.

    PubMed  CAS  Google Scholar 

  43. Fechner, H., A. Haack, H. Wang, X. Wang, K. Eizema, M. Pauschinger, R. Schoemaker, R. Veghel, A. Houtsmuller, H. P. Schultheiss, J. Lamers, and W. Poller. Expression of coxsackie adenovirus receptor and alphav-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers. Gene Ther. 6:1520–1535, 1999.

    Article  PubMed  CAS  Google Scholar 

  44. Fung, L. K., and W. M. Saltzman. Polymeric implants for cancer chemotherapy. Adv. Drug Deliv. Rev. 26:209–230, 1997.

    Article  PubMed  CAS  Google Scholar 

  45. Gabizon, A., R. Isacson, E. Libson, B. Kaufman, B. Uziely, R. Catane, C. G. Ben-Dor, E. Rabello, Y. Cass, T. Peretz, et al. Clinical studies of liposome-encapsulated doxorubicin. Acta Oncol. 33:779–786, 1994.

    PubMed  CAS  Google Scholar 

  46. Galanis, E., R. Vile, and S. J. Russell. Delivery systems intended for in vivo gene therapy of cancer: Targeting and replication competent viral vectors. Crit. Rev. Oncol. Hematol. 38:177–192, 2001.

    PubMed  CAS  Google Scholar 

  47. Garver, R. I., Jr., K. T. Goldsmith, B. Rodu, P. C. Hu, E. J. Sorscher, and D. T. Curiel. Strategy for achieving selective killing of carcinomas. Gene Ther. 1:46–50, 1994.

    PubMed  CAS  Google Scholar 

  48. Ghose, T., and A. H. Blair. Antibody-linked cytotoxic agents in the treatment of cancer: Current status and future prospects. J. Natl. Cancer Inst. 61:657–676, 1978.

    PubMed  CAS  Google Scholar 

  49. Goldenberg, D. M. Advancing role of radiolabeled antibodies in the therapy of cancer. Cancer Immunol. Immunother. 52:281–296, 2003.

    PubMed  CAS  Google Scholar 

  50. Goldman, C. K., B. E. Rogers, J. T. Douglas, B. A. Sosnowski, W. Ying, G. P. Siegal, A. Baird, J. A. Campain, and D. T. Curiel. Targeted gene delivery to Kaposi's sarcoma cells via the fibroblast growth factor receptor. Cancer Res. 57:1447–1451, 1997.

    PubMed  CAS  Google Scholar 

  51. Gollan, T. J., and M. R. Green. Selective targeting and inducible destruction of human cancer cells by retroviruses with envelope proteins bearing short peptide ligands. J. Virol. 76:3564–3569, 2002.

    Article  PubMed  CAS  Google Scholar 

  52. Gomez-Navarro, J., D. T. Curiel, and J. T. Douglas. Gene therapy for cancer. Eur. J. Cancer 35:867–885, 1999.

    Article  PubMed  CAS  Google Scholar 

  53. Gossen, M., and H. Bujard. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. U.S.A. 89:5547–5551, 1992.

    PubMed  CAS  Google Scholar 

  54. Greco, O., B. Marples, M. C. Joiner, and S. D. Scott. How to overcome (and exploit) tumor hypoxia for targeted gene therapy. J. Cell Physiol. 197:312–325, 2003.

    Article  PubMed  CAS  Google Scholar 

  55. Green, N. K., C. W. Herbert, S. J. Hale, A. B. Hale, V. Mautner, R. Harkins, T. Hermiston, K. Ulbrich, K. D. Fisher, and L. W. Seymour. Extended plasma circulation time and decreased toxicity of polymer-coated adenovirus. Gene Ther. 11:1256–1263, 2004.

    Article  PubMed  CAS  Google Scholar 

  56. Grimm, D., S. Zhou, H. Nakai, C. E. Thomas, T. A. Storm, S. Fuess, T. Matsushita, J. Allen, R. Surosky, M. Lochrie, L. Meuse, A. McClelland, P. Colosi, and M. A. Kay. Preclinical in vivo evaluation of pseudotyped adeno-associated virus vectors for liver gene therapy. Blood 102:2412–2419, 2003.

    Article  PubMed  CAS  Google Scholar 

  57. Groot-Wassink, T., E. O. Aboagye, M. Glaser, N. R. Lemoine, and G. Vassaux. Adenovirus biodistribution and noninvasive imaging of gene expression in vivo by positron emission tomography using human sodium/iodide symporter as reporter gene. Hum. Gene Ther. 13:1723–1735, 2002.

    Article  PubMed  CAS  Google Scholar 

  58. Hackett, N. R., T. El Sawy, L. Y. Lee, I. Silva, J. O'Leary, T. K. Rosengart, and R. G. Crystal. Use of quantitative TaqMan real-time PCR to track the time-dependent distribution of gene transfer vectors in vivo. Mol. Ther. 2:649–656, 2000.

    Article  PubMed  CAS  Google Scholar 

  59. Hahn, W. C., and R. A. Weinberg. Modelling the molecular circuitry of cancer. Nat. Rev. Cancer 2:331–341, 2002.

    Article  PubMed  CAS  Google Scholar 

  60. Hallahan, D. E., H. J. Mauceri, L. P. Seung, E. J. Dunphy, J. D. Wayne, N. N. Hanna, A. Toledano, S. Hellman, D. W. Kufe, and R. R. Weichselbaum. Spatial and temporal control of gene therapy using ionizing radiation. Nat. Med. 1:786–791, 1995.

    Article  PubMed  CAS  Google Scholar 

  61. Harris, J. D., A. A. Gutierrez, H. C. Hurst, K. Sikora, and N. R. Lemoine. Gene therapy for cancer using tumour-specific prodrug activation. Gene Ther. 1:170–175, 1994.

    PubMed  CAS  Google Scholar 

  62. Harrison, M., D. Tomlinson, and S. Stewart. Liposomal-entrapped doxorubicin: An active agent in AIDS-related Kaposi's sarcoma. J. Clin. Oncol. 13:914–920, 1995.

    PubMed  CAS  Google Scholar 

  63. Hashizume, H., P. Baluk, S. Morikawa, J. W. McLean, G. Thurston, S. Roberge, R. K. Jain, and D. M. McDonald. Openings between defective endothelial cells explain tumor vessel leakiness. Am. J. Pathol. 156:1363–1380, 2000.

    PubMed  CAS  Google Scholar 

  64. Haviv, Y. S., and D. T. Curiel. Conditional gene targeting for cancer gene therapy. Adv. Drug Deliv. Rev. 53:135–154, 2001.

    Article  PubMed  CAS  Google Scholar 

  65. Hegenbarth, S., R. Gerolami, U. Protzer, P. L. Tran, C. Brechot, G. Gerken, and P. A. Knolle. Liver sinusoidal endothelial cells are not permissive for adenovirus type 5. Hum. Gene Ther. 11:481–486, 2000.

    Article  PubMed  CAS  Google Scholar 

  66. Helmlinger, G., F. Yuan, M. Dellian, and R. K. Jain. Interstitial pH and pO2 gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation. Nature Med. 3:177–182, 1997.

    Article  PubMed  CAS  Google Scholar 

  67. Herman, S., G. Hooftman, and E. Schacht. Poly(Ethylene Glycol) with Reactive Endgroups.1. Modification of Proteins. J. Bioact. Compat. Pol. 10:145–187, 1995.

    CAS  Google Scholar 

  68. Hermens, W. T., and J. Verhaagen. Viral vectors, tools for gene transfer in the nervous system. Prog. Neurobiol. 55:399–432, 1998.

    Article  PubMed  CAS  Google Scholar 

  69. Herz, J., and R. D. Gerard. Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice. Proc. Natl. Acad. Sci. U.S.A. 90:2812–2816, 1993.

    PubMed  CAS  Google Scholar 

  70. Hobbs, S. K., W. Monsky, F. Yuan, W. G. Roberts, L. Griffith, V. P. Torchillin, and R. K. Jain. Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. Proc. Nat. Acad. Sci. U.S.A. 95:4607–4612, 1998.

    Article  CAS  Google Scholar 

  71. Hooftman, G., S. Herman, and E. Schacht. Poly(ethylene glycol)s with reactive endgroups.2. Practical consideration for the preparation of protein-PEG conjugates. J. Bioact. Compat. Pol. 11:135–159, 1996.

    CAS  Google Scholar 

  72. Huang, Q., J. K. Hu, F. Lohr, L. Zhang, R. Braun, J. Lanzen, J. B. Little, M. W. Dewhirst, and C. Y. Li. Heat-induced gene expression as a novel targeted cancer gene therapy strategy. Cancer Res. 60:3435–3439, 2000.

    PubMed  CAS  Google Scholar 

  73. Huard, J., H. Lochmuller, G. Acsadi, A. Jani, B. Massie, and G. Karpati. The route of administration is a major determinant of the transduction efficiency of rat tissues by adenoviral recombinants. Gene Ther. 2:107–115, 1995.

    PubMed  CAS  Google Scholar 

  74. Jaggar, R. T., H. Y. Chan, A. L. Harris, and R. Bicknell. Endothelial cell-specific expression of tumor necrosis factor-alpha from the KDR or E-selectin promoters following retroviral delivery. Hum. Gene Ther. 8:2239–2247, 1997.

    PubMed  CAS  Google Scholar 

  75. Jain, R. K. Transport of molecules in the tumor interstitium: A review. Cancer Res. 47:3039–3051, 1987.

    PubMed  CAS  Google Scholar 

  76. Jain, R. K. Determinants of tumor blood flow: A review. Cancer Res. 48:2641–2658, 1988.

    PubMed  CAS  Google Scholar 

  77. Jain, R. K. Delivery of molecular and cellular medicine to solid tumors. Adv. Drug Deliv. Rev. 26:71–90, 1997.

    Article  PubMed  CAS  Google Scholar 

  78. Jain, R. K. The next frontier of molecular medicine—Delivery of therapeutics. Nat. Med. 4:655–657, 1998.

    Article  PubMed  CAS  Google Scholar 

  79. Jenster, G., T. E. Spencer, M. M. Burcin, S. Y. Tsai, M. J. Tsai, and B. W. O'Malley. Steroid receptor induction of gene transcription: A two-step model. Proc. Natl. Acad. Sci. U.S.A. 94:7879–7884, 1997.

    Article  PubMed  CAS  Google Scholar 

  80. Joki, T., M. Nakamura, and T. Ohno. Activation of the radiosensitive EGR-1 promoter induces expression of the herpes simplex virus thymidine kinase gene and sensitivity of human glioma cells to ganciclovir. Hum. Gene Ther. 6:1507–1513, 1995.

    PubMed  CAS  Google Scholar 

  81. Jooss, K., and N. Chirmule. Immunity to adenovirus and adeno-associated viral vectors: Implications for gene therapy. Gene Ther. 10:955–963, 2003.

    Article  PubMed  CAS  Google Scholar 

  82. Juweid, M., R. Neumann, C. Paik, M. J. Perez-Bacete, J. Sato, W. van Osdol, and J. N. Weinstein. Micropharmacology of monoclonal antibodies in solid tumors: Direct experimental evidence for a binding site barrier. Cancer Res. 52:5144–5153, 1992.

    PubMed  CAS  Google Scholar 

  83. Kass-Eisler, A., E. Falck-Pedersen, D. H. Elfenbein, M. Alvira, P. M. Buttrick, and L. A. Leinwand. The impact of developmental stage, route of administration and the immune system on adenovirus-mediated gene transfer. Gene Ther. 1:395–402, 1994.

    PubMed  CAS  Google Scholar 

  84. Kay, M. A., J. C. Glorioso, and L. Naldini. Viral vectors for gene therapy: The art of turning infectious agents into vehicles of therapeutics. Nat Med. 7:33–40, 2001.

    Article  PubMed  CAS  Google Scholar 

  85. Kirn, A., J. P. Gut, and J. L. Gendrault. Interaction of viruses with sinusoidal cells. Prog. Liver Dis. 7:377–392, 1982.

    PubMed  CAS  Google Scholar 

  86. Kizaka-Kondoh, S., M. Inoue, H. Harada, and M. Hiraoka. Tumor hypoxia: A target for selective cancer therapy. Cancer Sci. 94:1021–1028, 2003.

    Article  PubMed  CAS  Google Scholar 

  87. Kong, G., R. D. Braun, and M. W. Dewhirst. Hyperthermia enables tumor-specific nanoparticle delivery: Effect of particle size. Cancer Res. 60:4440–4445, 2000.

    PubMed  CAS  Google Scholar 

  88. Kong, H. L., and R. G. Crystal. Gene therapy strategies for tumor antiangiogenesis. J. Natl. Cancer Inst. 90:273–286, 1998.

    Article  PubMed  CAS  Google Scholar 

  89. Koshikawa, N., K. Takenaga, M. Tagawa, and S. Sakiyama. Therapeutic efficacy of the suicide gene driven by the promoter of vascular endothelial growth factor gene against hypoxic tumor cells. Cancer Res 60:2936–2941, 2000.

    PubMed  CAS  Google Scholar 

  90. Krol, A., J. Maresca, M. W. Dewhirst, and F. Yuan. Available volume fraction of macromolecules in the extravascular space of a fibrosarcoma: Implications for drug delivery. Cancer Res. 59:4136–4141, 1999.

    PubMed  CAS  Google Scholar 

  91. Kroll, R. A., M. A. Pagel, L. L. Muldoon, S. Roman-Goldstein, and E. A. Neuwelt. Increasing volume of distribution to the brain with interstitial infusion: Dose, rather than convection, might be the most important factor. Neurosurgery 38:746–752; discussion 752–754, 1996.

    Article  PubMed  CAS  Google Scholar 

  92. Kumagai, T., Y. Tanio, T. Osaki, S. Hosoe, I. Tachibana, K. Ueno, T. Kijima, T. Horai, and T. Kishimoto. Eradication of Myc-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements. Cancer Res. 56:354–358, 1996.

    PubMed  CAS  Google Scholar 

  93. Kuznetsov, Y. G., J. G. Victoria, A. Low, W. E. Robinson Jr., H. Fan, and A. McPherson. Atomic force microscopy imaging of retroviruses: Human immunodeficiency virus and murine leukemia virus. Scanning 26:209–216, 2004.

    Article  PubMed  CAS  Google Scholar 

  94. Lanciotti, J., A. Song, J. Doukas, B. Sosnowski, G. Pierce, R. Gregory, S. Wadsworth, and C. O'Riordan. Targeting adenoviral vectors using heterofunctional polyethylene glycol FGF2 conjugates. Mol. Ther. 8:99–107, 2003.

    Article  PubMed  CAS  Google Scholar 

  95. Langer, R. New methods of drug delivery. Science 249:1527–1533, 1990.

    PubMed  CAS  Google Scholar 

  96. Lee, Y. T. Breast carcinoma: Pattern of metastasis at autopsy. J. Surg. Oncol. 23:175–180, 1983.

    PubMed  CAS  Google Scholar 

  97. Li, E., S. L. Brown, D. G. Stupack, X. S. Puente, D. A. Cheresh, and G. R. Nemerow. Integrin alpha(v)beta1 is an adenovirus coreceptor. J. Virol. 75:5405–5409, 2001.

    Article  PubMed  CAS  Google Scholar 

  98. Li, E., S. L. Brown, D. J. Von Seggern, G. B. Brown, and G. R. Nemerow. Signaling antibodies complexed with adenovirus circumvent CAR and integrin interactions and improve gene delivery. Gene Ther. 7:1593–1599, 2000.

    Article  PubMed  CAS  Google Scholar 

  99. Lieberman, D. M., D. W. Laske, P. F. Morrison, K. S. Bankiewicz, and E. H. Oldfield. Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion. J. Neurosurg. 82:1021–1029, 1995.

    PubMed  CAS  Google Scholar 

  100. Lowenstein, P. R. Virology and immunology of gene therapy, or virology and immunology of high MOI infection with defective viruses. Gene Ther. 10:933–934, 2003.

    Article  PubMed  CAS  Google Scholar 

  101. Lu, Y., J. Carraher, Y. Zhang, J. Armstrong, J. Lerner, W. P. Rogers, and M. S. Steiner. Delivery of adenoviral vectors to the prostate for gene therapy. Cancer Gene Ther. 6:64–72, 1999.

    Article  PubMed  CAS  Google Scholar 

  102. Lund, A. H., and M. van Lohuizen. Epigenetics and cancer. Genes Dev. 18:2315–2335, 2004.

    Article  PubMed  CAS  Google Scholar 

  103. Luo, D., and W. M. Saltzman. Synthetic DNA delivery systems. Nat. Biotechnol. 18:33–37, 2000.

    Article  PubMed  CAS  Google Scholar 

  104. Mak, M., L. Fung, J. Strasser, and W. M. Saltzman. Distribution of drugs following controlled delivery to the brain interstitium. J. Neuro-Oncol. 26:91–102, 1995.

    Article  CAS  Google Scholar 

  105. Martin, F., S. Chowdhury, S. Neil, N. Phillipps, and M. K. Collins. Envelope-targeted retrovirus vectors transduce melanoma xenografts but not spleen or liver. Mol. Ther. 5:269–274, 2002.

    Article  PubMed  CAS  Google Scholar 

  106. Martin, F., S. Neil, J. Kupsch, M. Maurice, F. Cosset, and M. Collins. Retrovirus targeting by tropism restriction to melanoma cells. J. Virol. 73:6923–6929, 1999.

    PubMed  CAS  Google Scholar 

  107. McCormack, J. E., W. Edwards, J. Sensintaffer, L. Lillegren, M. Kozloski, D. Brumm, L. Karavodin, D. J. Jolly, and J. Greengard. Factors affecting long-term expression of a secreted transgene product after intravenous administration of a retroviral vector. Mol. Ther. 3:516–525, 2001.

    Article  PubMed  CAS  Google Scholar 

  108. McGuire, S. Quantitative Analysis of Intriatumoral Infusion Therapy and Macromolecule Movement in Tumor Tissue. Biomedical Engineering: Durham, Duke University, 2004.

    Google Scholar 

  109. McGuire, S., and F. Yuan. Quantitative analysis of intratumoral infusion of color molecules. Am. J. Physiol. Heart Circ. Physiol. 281: H715–H721, 2001.

    PubMed  CAS  Google Scholar 

  110. McGuire, S., D. Zaharoff, and F. Yuan. Interstitial transport of macromolecules: Implication for nucleic acid delivery in solid tumors. In: Pharmaceutical Perspectives of Nucleic Acid-Based Therapeutics, edited by R. I. Mahato and S. W. Kim. London: Taylor & Francis, 2002, pp. 434–454.

    Google Scholar 

  111. Medina-Kauwe, L. K. Endocytosis of adenovirus and adenovirus capsid proteins. Adv. Drug Deliv. Rev. 55:1485–1496, 2003.

    Article  PubMed  CAS  Google Scholar 

  112. Mesnil, M., and H. Yamasaki. Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene therapy: Role of gap-junctional intercellular communication. Cancer Res. 60:3989–3999, 2000.

    PubMed  CAS  Google Scholar 

  113. Morrison, P. F., D. W. Laske, H. Bobo, E. H. Oldfield, and R. L. Dedrick. High-flow microinfusion: Tissue penetration and pharmacodynamics. Am. J. Physiol. 266: R292–R305, 1994.

    PubMed  CAS  Google Scholar 

  114. Nasu, Y., C. H. Bangma, G. W. Hull, H. M. Lee, J. Hu, J. Wang, M. A. McCurdy, S. Shimura, G. Yang, T. L. Timme, and T. C. Thompson. Adenovirus-mediated interleukin-12 gene therapy for prostate cancer: Suppression of orthotopic tumor growth and pre-established lung metastases in an orthotopic model. Gene Ther. 6:338–349, 1999.

    Article  PubMed  CAS  Google Scholar 

  115. Nemunaitis, J., F. Khuri, I. Ganly, J. Arseneau, M. Posner, E. Vokes, J. Kuhn, T. McCarty, S. Landers, A. Blackburn, L. Romel, B. Randlev, S. Kaye, and D. Kirn. Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J. Clin. Oncol. 19:289–298, 2001.

    PubMed  CAS  Google Scholar 

  116. Nettelbeck, D. M., V. Jerome, and R. Muller. Gene therapy: Designer promoters for tumour targeting. Trends Genet. 16:174–181, 2000.

    Article  PubMed  CAS  Google Scholar 

  117. O'Riordan, C. R., A. Lachapelle, C. Delgado, V. Parkes, S. C. Wadsworth, A. E. Smith, and G. E. Francis. PEGylation of adenovirus with retention of infectivity and protection from neutralizing antibody in vitro and in vivo. Hum. Gene Ther. 10:1349–1358, 1999.

    Article  PubMed  Google Scholar 

  118. Paielli, D. L., M. S. Wing, K. R. Rogulski, J. D. Gilbert, A. Kolozsvary, J. H. Kim, J. Hughes, M. Schnell, T. Thompson, and S. O. Freytag. Evaluation of the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent human adenovirus following intraprostatic administration in the mouse. Mol. Ther. 1:263–274, 2000.

    Article  PubMed  CAS  Google Scholar 

  119. Pan, D., R. Gunther, W. Duan, S. Wendell, W. Kaemmerer, T. Kafri, I. M. Verma, and C. B. Whitley. Biodistribution and toxicity studies of VSVG-pseudotyped lentiviral vector after intravenous administration in mice with the observation of in vivo transduction of bone marrow. Mol. Ther. 6:19–29, 2002.

    Article  PubMed  CAS  Google Scholar 

  120. Pannier, A. K., and L. D. Shea. Controlled release systems for DNA delivery. Mol. Ther. 10:19–26, 2004.

    Article  PubMed  CAS  Google Scholar 

  121. Pasut, G., A. Guiotto, and F. Veronese. Protein, peptide and non-peptide drug PEGylation for therapeutic application. Expert Opin. Ther. Pat. 14:859–894, 2004.

    Article  CAS  Google Scholar 

  122. Pelkmans, L., and A. Helenius. Insider information: What viruses tell us about endocytosis. Curr. Opin. Cell Biol. 15:414–422, 2003.

    Article  PubMed  CAS  Google Scholar 

  123. Peng, K. W., F. J. Morling, F. L. Cosset, G. Murphy, and S. J. Russell. A gene delivery system activatable by disease-associated matrix metalloproteinases. Hum. Gene Ther. 8:729–738, 1997.

    Article  PubMed  CAS  Google Scholar 

  124. Peng, K. W., R. Vile, F. L. Cosset, and S. Russell. Selective transduction of protease-rich tumors by matrix-metalloproteinase-targeted retroviral vectors. Gene Ther. 6:1552–1557, 1999.

    Article  PubMed  CAS  Google Scholar 

  125. Pollock, R., R. Issner, K. Zoller, S. Natesan, V. M. Rivera, and T. Clackson. Delivery of a stringent dimerizer-regulated gene expression system in a single retroviral vector. Proc. Natl. Acad. Sci. U.S.A. 97:13221–13226, 2000.

    Article  PubMed  CAS  Google Scholar 

  126. Printz, M. A., A. M. Gonzalez, M. Cunningham, D. L. Gu, M. Ong, G. F. Pierce, and S. L. Aukerman. Fibroblast growth factor 2-retargeted adenoviral vectors exhibit a modified biolocalization pattern and display reduced toxicity relative to native adenoviral vectors. Hum. Gene Ther. 11:191–204, 2000.

    Article  PubMed  CAS  Google Scholar 

  127. Putnam, D., C. A. Gentry, D. W. Pack, and R. Langer. Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini. Proc. Natl. Acad. Sci. U.S.A. 98:1200–1205, 2001.

    Article  PubMed  CAS  Google Scholar 

  128. Rader, C., and B. List. Catalytic antibodies as magic bullets. Chemistry 6:2091–5, 2000.

    Article  PubMed  CAS  Google Scholar 

  129. Renkin, E. M. Cellular and intercellular transport pathways in exchange vessels. Am. Rev. Respir. Dis. 146: S28–S31, 1992.

    PubMed  CAS  Google Scholar 

  130. Reynolds, P. N., K. R. Zinn, V. D. Gavrilyuk, I. V. Balyasnikova, B. E. Rogers, D. J. Buchsbaum, M. H. Wang, D. J. Miletich, W. E. Grizzle, J. T. Douglas, S. M. Danilov, and D. T. Curiel. A targetable, injectable adenoviral vector for selective gene delivery to pulmonary endothelium in vivo. Mol. Ther. 2:562–578, 2000.

    Article  PubMed  CAS  Google Scholar 

  131. Richardson, T. B., J. Kaspers, and C. D. Porter. Retroviral hybrid LTR vector strategy: Functional analysis of LTR elements and generation of endothelial cell specificity. Gene Ther. 11:775–783, 2004.

    Article  PubMed  CAS  Google Scholar 

  132. Rogers, B. E., J. T. Douglas, C. Ahlem, D. J. Buchsbaum, J. Frincke, and D. T. Curiel. Use of a novel cross-linking method to modify adenovirus tropism. Gene Ther. 4:1387–1392, 1997.

    Article  PubMed  CAS  Google Scholar 

  133. Rooseboom, M., J. N. Commandeur, and N. P. Vermeulen. Enzyme-catalyzed activation of anticancer prodrugs. Pharmacol. Rev. 56:53–102, 2004.

    Article  PubMed  CAS  Google Scholar 

  134. Roth, J. A., and R. J. Cristiano. Gene therapy for cancer: What have we done and where are we going? J. Natl. Cancer Inst. 89:21–39, 1997.

    Article  PubMed  CAS  Google Scholar 

  135. Ruan, H., and D. F. Deen. Use of hypoxia-regulated gene expression in tumor-specific gene therapy. Curr. Opin. Invest. Drugs 2:839–843, 2001.

    CAS  Google Scholar 

  136. Sauthoff, H., J. Hu, C. Maca, M. Goldman, S. Heitner, H. Yee, T. Pipiya, W. N. Rom, and J. G. Hay. Intratumoral spread of wild-type adenovirus is limited after local injection of human xenograft tumors: Virus persists and spreads systemically at late time points. Hum. Gene Ther. 14:425–433, 2003.

    Article  PubMed  CAS  Google Scholar 

  137. Schellingerhout, D., A. Bogdanov, Jr., E. Marecos, M. Spear, X. Breakefield, and R. Weissleder. Mapping the in vivo distribution of herpes simplex virions. Hum. Gene Ther. 9:1543–1549, 1998.

    PubMed  CAS  Google Scholar 

  138. Scherphof, G., F. Roerdink, J. Dijkstra, H. Ellens, R. de Zanger, and E. Wisse. Uptake of liposomes by rat and mouse hepatocytes and Kupffer cells. Biol. Cell 47:47–57, 1983.

    Google Scholar 

  139. Senter, P. D., and C. J. Springer. Selective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates. Adv. Drug Deliv. Rev. 53:247–264, 2001.

    Article  PubMed  CAS  Google Scholar 

  140. Seth, P. Adenoviral vectors. In: Cancer Gene Therapy: Past Achievements and Future Challenges, edited by H. Kluwer. New York: Academic Publishers, 2000, pp. 13–22.

    Google Scholar 

  141. Shannon, A. M., D. J. Bouchier-Hayes, C. M. Condron, and D. Toomey. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat. Rev. 29:297–307, 2003.

    Article  PubMed  CAS  Google Scholar 

  142. Shea, L. D., E. Smiley, J. Bonadio, and D. J. Mooney. DNA delivery from polymer matrices for tissue engineering. Nat. Biotechnol. 17:551–554, 1999.

    Article  PubMed  CAS  Google Scholar 

  143. Shiratori, Y., M. Tananka, T. Kawase, S. Shiina, Y. Komatsu, and M. Omata. Quantification of sinusoidal cell function in vivo. Semin. Liver Dis. 13:39–49, 1993.

    Article  PubMed  CAS  Google Scholar 

  144. Smith, A., and A. Helenius. How viruses enter animal cells. Science 304:237–242, 2004.

    Article  PubMed  CAS  Google Scholar 

  145. Smith, S. A., and G. J. Kotwal. Immune response to poxvirus infections in various animals. Crit. Rev. Microbiol. 28:149–185, 2002.

    Article  PubMed  Google Scholar 

  146. Staba, M. J., H. J. Mauceri, D. W. Kufe, D. E. Hallahan, and R. R. Weichselbaum. Adenoviral TNF-alpha gene therapy and radiation damage tumor vasculature in a human malignant glioma xenograft. Gene Ther. 5:293–300, 1998.

    Article  PubMed  CAS  Google Scholar 

  147. Tang, D. C., S. A. Johnston, and D. P. Carbone. Butyrate-inducible and tumor-restricted gene expression by adenovirus vectors. Cancer Gene Ther. 1:15–20, 1994.

    PubMed  CAS  Google Scholar 

  148. Thomas, C. E., A. Ehrhardt, and M. A. Kay. Progress and problems with the use of viral vectors for gene therapy. Nat. Rev. Genet. 4:346–358, 2003.

    Article  PubMed  CAS  Google Scholar 

  149. Tjuvajev, J. G., S. H. Chen, A. Joshi, R. Joshi, Z. S. Guo, J. Balatoni, D. Ballon, J. Koutcher, R. Finn, S. L. Woo, and R. G. Blasberg. Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo. Cancer Res. 59:5186–5193, 1999.

    PubMed  CAS  Google Scholar 

  150. Toloza, E. M., K. Hunt, S. Swisher, W. McBride, R. Lau, S. Pang, K. Rhoades, T. Drake, A. Belldegrun, J. Glaspy, and J. S. Economou. In vivo cancer gene therapy with a recombinant interleukin-2 adenovirus vector. Cancer Gene Ther. 3:11–17, 1996.

    PubMed  CAS  Google Scholar 

  151. Verma, I. M., and N. Somia. Gene therapy—Promises, problems and prospects. Nature 389:239–242, 1997.

    Article  PubMed  CAS  Google Scholar 

  152. Vogelstein, B., and K. W. Kinzler. Cancer genes and the pathways they control. Nature Med. 10:789–799, 2004.

    Article  PubMed  CAS  Google Scholar 

  153. von Mehren, M., G. P. Adams, and L. M. Weiner. Monoclonal antibody therapy for cancer. Annu. Rev. Med. 54:343–369, 2003.

    Article  PubMed  CAS  Google Scholar 

  154. Vrancken Peeters, M. J., A. L. Perkins, and M. A. Kay. Method for multiple portal vein infusions in mice: Quantitation of adenovirus-mediated hepatic gene transfer. Biotechniques 20:278–285, 1996.

    PubMed  CAS  Google Scholar 

  155. Wang, Y., J. K. Hu, A. Krol, Y. P. Li, C. Y. Li, and F. Yuan. Systemic dissemination of viral vectors during intratumoral injection. Mol. Cancer Ther. 2:1233–1242, 2003.

    PubMed  CAS  Google Scholar 

  156. Wang, Y., Z. Yang, S. Liu, T. Kon, A. Krol, C. Y. Li, and F. Yuan. Characterization of systemic dissemination of non-replicating adenoviral vectors from tumors in gene delivery. Br. J. Cancer 92:1414–1420, 2004.

    Article  CAS  Google Scholar 

  157. Wickham, T. J., D. M. Segal, P. W. Roelvink, M. E. Carrion, A. Lizonova, G. M. Lee, and I. Kovesdi. Targeted adenovirus gene transfer to endothelial and smooth muscle cells by using bispecific antibodies. J. Virol. 70:6831–6838, 1996.

    PubMed  CAS  Google Scholar 

  158. Wood, M., P. Perrotte, E. Onishi, M. E. Harper, C. Dinney, L. Pagliaro, and D. R. Wilson. Biodistribution of an adenoviral vector carrying the luciferase reporter gene following intravesical or intravenous administration to a mouse. Cancer Gene Ther. 6:367–372, 1999.

    Article  PubMed  CAS  Google Scholar 

  159. Wu, N. Z., D. Da, T. L. Rudoll, D. Needham, A. R. Whorton, and M. W. Dewhirst. Increased microvascular permeability contributes to preferential accumulation of stealth liposomes in tumor tissue. Cancer Res. 53:3765–3770, 1993.

    PubMed  CAS  Google Scholar 

  160. Yoon, S. K., L. Mohr, C. R. O'Riordan, A. Lachapelle, D. Armentano, and J. R. Wands. Targeting a recombinant adenovirus vector to HCC cells using a bifunctional Fab-antibody conjugate. Biochem. Biophys. Res. Commun. 272:497–504, 2000.

    Article  PubMed  CAS  Google Scholar 

  161. Yoshida, Y., A. Sadata, W. Zhang, K. Saito, N. Shinoura, and H. Hamada. Generation of fiber-mutant recombinant adenoviruses for gene therapy of malignant glioma. Hum. Gene Ther. 9:2503–2515, 1998.

    Article  PubMed  CAS  Google Scholar 

  162. You, L., and J. Yin. Amplification and spread of viruses in a growing plaque. J. Theor. Biol. 200:365–373, 1999.

    Article  PubMed  CAS  Google Scholar 

  163. Yuan, F. Transvascular drug delivery in solid tumors. Semin. Radiat. Oncol. 8:164–175, 1998.

    PubMed  CAS  Google Scholar 

  164. Yuan, F., M. Dellian, D. Fukumura, M. Leunig, D. A. Berk, V. P. Torchilin, and R. K. Jain. Vascular permeability in a human tumor xenograft: Molecular size dependence and cutoff size. Cancer Res. 55:3752–3756, 1995.

    PubMed  CAS  Google Scholar 

  165. Yuan, F., A. Krol, and S. Tong. Available space and extracellular transport of macromolecules: Effects of pore size and connectedness. Ann. Biomed. Eng. 29:1150–1158, 2001.

    Article  PubMed  CAS  Google Scholar 

  166. Yuan, F., M. Leunig, S. K. Huang, D. A. Berk, D. Papahadjopoulos, and R. K. Jain. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res. 54:3352–3356, 1994.

    PubMed  CAS  Google Scholar 

  167. Yuan, F., H. A. Salehi, Y. Boucher, U. S. Vasthare, R. F. Tuma, and R. K. Jain. Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows. Cancer Res. 54:4564–4568, 1994.

    PubMed  CAS  Google Scholar 

  168. Zhang, L., P. J. Dailey, A. Gettie, J. Blanchard, and D. D. Ho. The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys. J. Virol. 76:5271–5273, 2002.

    Article  PubMed  CAS  Google Scholar 

  169. Zhang, X. Y., J. Luck, M. W. Dewhirst, and F. Yuan. Interstitial hydraulic conductivity in a fibrosarcoma. Am. J. Physiol. Heart Circ. Physiol. 279: H2726–H2734, 2000.

    PubMed  CAS  Google Scholar 

  170. Zinn, K. R., J. T. Douglas, C. A. Smyth, H. G. Liu, Q. Wu, V. N. Krasnykh, J. D. Mountz, D. T. Curiel, and J. M. Mountz. Imaging and tissue biodistribution of 99mTc-labeled adenovirus knob (serotype 5). Gene Ther. 5:798–808, 1998.

    Article  PubMed  CAS  Google Scholar 

  171. Wang, Y., S. Liu, C.-Y. Li, and F. Yuan. A novel method for viral gene delivery in solid tumors. Cancer Res. 65:7541–7545, 2005.

    Google Scholar 

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ACKNOWLEDGMENTS

The authors thank Dr Chuan-Yuan Li for scientific discussion. The work is supported in part by a grant from the National Science Foundation (BES-9984062).

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  1. Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA

    Yong Wang & Fan Yuan

  2. Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC, 27708, USA

    Fan Yuan

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Wang, Y., Yuan, F. Delivery of Viral Vectors to Tumor Cells: Extracellular Transport, Systemic Distribution, and Strategies for Improvement. Ann Biomed Eng 34, 114–127 (2006). https://doi.org/10.1007/s10439-005-9007-2

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