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Drug Targeting pp 255-304 | Cite as

15 Targeted Gene Transfer

A Practical Guide Based on Experience with Lipid-Based Plasmid Delivery Systems
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Part of the Methods in Molecular Medicine™ book series (MIMM, volume 25)

Abstract

The overall goal of gene therapy is to cure or stabilize a disease process that results from the production of a mutant protein (for example, the chloride channel protein important in cystic fibrosis) or overproduction of a normal protein (such as the products of certain oncogenes). We can achieve this goal by replacing the defective gene or by reducing the overexpression of the target gene using an antisense strategy, thus reducing the production of the diseasepromoting protein (1,2). For either method, it is critical to transfer DNA into target cells in a concentration high enough to be effective in modifying the disease. DNA must be delivered to the desired cell population in an intact state, whereby it can be efficiently transcribed and ultimately translated. The method of gene transfer must be highly efficient and nontoxic, and the delivery system must be relatively easy to prepare and administer (3). There is a great deal of optimism surrounding the development of gene therapy as an effective strategy for management of many different human diseases. The active agent used to procure gene therapy is likely to consist of oligonucleotides, ribozymes, or a DNA sequence that can be transcribed into a message capable of eliciting a therapeutic response. Unlike conventional small-molecule therapeutics however, gene therapy requires the use of a carrier system to deliver the active agent directly into the target cell population.

Keywords

Luria Broth Cationic Lipid Cationic Liposome Cesium Chloride Lipid Marker 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Sokol, D. L. and Gewirtz, A. M. (1996) Gene therapy: basic concepts and recent advances. Crit. Rev. Euk. Gene Express. 6(1), 29–57.Google Scholar
  2. 2.
    Roth, J. A. and Cristiano, R. J. (1991) Gene therapy for cancer: what have we done and where are we going? J. Natl. Cancer Inst. 89(1), 21–39.Google Scholar
  3. 3.
    Bertling, W. A., Gareis, M., Paspaleeva, V., Zimmer, A., Kreuter, J., Numberg, E., and Harrer, P. (1991) Use of liposomes, viral capsids and nanoparticles as DNA carriers. Biotech. Appl. Biochem. 13, 390–405.Google Scholar
  4. 4.
    Cooper, M. J. (1996) Noninfectious gene transfer and expression systems for cancer gene therapy. Sem. Oncol. 23(1), 172–187.Google Scholar
  5. 5.
    Ledley, F. D. (1995) Nonviral gene therapy: the promise of genes as pharmaceu-tical products. Hum. Gene Ther. 6, 1129–1144.PubMedGoogle Scholar
  6. 6.
    Tomlinson, E. and Rolland, A. P. (1996) Controllable gene therapy: pharmaceu-tics of non-viral gene delivery systems. J. Contr. Rel. 39, 357–372.Google Scholar
  7. 7.
    Nabel, E. G., Gordon, D., Yang, Z. Y., Xu, L., San, H., Plautz, G. E., Wu, B. Y., Gao, X., Huang L., and Nabel, G. J. (1992) Gene transfer in vivo with DNA-liposome complexes: lack of autoimmunity and gonadal localization. Hum. Gene Ther. 3, 649–656.PubMedGoogle Scholar
  8. 8.
    Nabel, G. J., Nabel, E. G., Yang, Z. Y., Fox, B.A., Plautz, G. E., Gao, X., Huang, L., Shu, S., Gordon, D., and Chang, A. E. (1992) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of tox-icity in humans. Proc. Natl. Acad. Sci. USA 90, 11,307–11,311.Google Scholar
  9. 9.
    Canonico, A. E., Plitman, J. D., Conary, J. T., Meyrick, B. O., and Brigham, K. L. (1994) No lung toxicity after repeated aerosol or intravenous delivery of plas-mid-cationic liposome complexes. J. Appl. Phys. 77(1), 415–419.Google Scholar
  10. 10.
    Bogdanov, A. A., Jr., Weissleder, R., Frank, H. W., Bogdanova, A. V., Nossif, N., Schaffer, B. K., Tsai, E., Papisov, M. I., and Brady, T. J. (1993) A new macromolecule as a contrast agent for MR angiography: preparation, properties, and animal studies. Radiol. 187(3), 701–706.Google Scholar
  11. 11.
    Chancerelle, Y., Mathieu, J., Viret-Soropogui, R., Tosetti, F., Alban, C., and Kergonou, J. F. (1993) Immunization of rabbits with proteins reacted with mal-onic dialdehyde (MDA): kinetics and specificity ofthe immune response. Biochem. Molec. Biol. Intl. 29(1), 141–148.Google Scholar
  12. 12.
    Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., Ringold, G. M., and Danielsen, M. (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfeGtion procedure. Proc. Natl. Acad. Sci. USA 84, 7413–7417.PubMedGoogle Scholar
  13. 13.
    Felgner, P. L. and Ringold, G. M. (1989) Cationic liposome-mediated transfec-tion. Nature 337(6205), 387,388.Google Scholar
  14. 14.
    Farhood, H., Gao, X., Son, K., Yang, Y.-Y., Lazo, J. S., Huang, L., Barsoum, J., Bottega, R., and Epand, R. (1994) Cationic liposomes for direct gene transfer in therapy of cancer and other diseases. Ann. NY Acad. Sci. 716, 23–35.PubMedGoogle Scholar
  15. 15.
    Caplen, N. J., Kinrade, E., Sorgi, F., Gao, X., Gruenert, D., Geddes, D., Coutelle, C., Huang, L., Alton, E. W., and Williamson, R. (1995) In vitro liposome-medi-ated DNA transfection of epithelial cell lines using the cationic liposome DC-Chol/DOPE. Gene Ther. 2, 603–613.PubMedGoogle Scholar
  16. 16.
    Gao, X. and Huang, L. (1996) Potentiation of cationic liposome-mediated gene delivery by polycations. Biochemistry 35(3), 1027–1036.PubMedGoogle Scholar
  17. 17.
    Zhang, Y.-P., Reimer, D. L., Zhang, G., Lee, P. H., and Bally, M. B. (1996) Self-assembling DNA-lipid particles for gene transfer. Pharmaceut. Res. 14(2), 190–196.Google Scholar
  18. 18.
    Behr, J. P., Demeneix, B., Loeffler, J.-P., and Perez-Mutul, J. (1989) Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA. Proc. Natl. Acad Sci USA 86, 6982–6986.PubMedGoogle Scholar
  19. 19.
    Wolfert, M. A., Schacht, E. J., Toncheva, V., Illbrich, K., Nazarova, O., and Seymour, L. W. (1996) Characterization of vectors for gene therapy formed by self assembly of DNA with synthetic block co-polymers. Hum. Gene Ther. 7(17), 2123–2133.PubMedGoogle Scholar
  20. 20.
    Barthel, F., Remy, J.-S., Loeffler, J.-P., and Behr, J.-P. (1993) Gene transfer optimization with liposperrnine:coated DNA. DNA Cell Biol. 12(6), 553–560.PubMedGoogle Scholar
  21. 21.
    Kabanov, A. V. and Kabanov, V. A. (1995) DNA complexes with polycations for the delivery of genetic material into cells. Bioconj. Chem. 6, 7–20.Google Scholar
  22. 22.
    Zhou, X, Klibanov, A., and Huang, L. (1991) Lipophile polylysines mediate efficient DNA transfection in mammalian cells. Biochim. Biophys. Acta 1065, 8–14.PubMedGoogle Scholar
  23. 23.
    Cotten, M., Langle-Rouault, F., Kirlappos, H., Wagner, E., Mechtler, K., Zenke, M., Beug, H., and Birnstiel, M. L. (1990) Transferrin-polycation-mediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. Proc. Natl. Acad. Sci. USA 87(11), 4033–4037.PubMedGoogle Scholar
  24. 24.
    Wagner, E., Zenke, M., Cotten, M., Beug, H., and Birnstiel, M. L. (1990) Trans-ferrin-polycation conjugates as carriers for DNA uptake into cells. Proc. Natl. Acad. Sci. USA 87(9), 3410–3414.PubMedGoogle Scholar
  25. 25.
    Zenke, M., Steinlein, P., Wagner, E., Cotten, M., Beug, H., and Birnstiel, M. L. (1990) Receptormediated endocytosis of transferrin-polycation conjugates: an efficient way to introduce DNA into hematopoietic cells. Proc. Natl. Acad. Sci. USA 87 (10), 3655–3659.PubMedGoogle Scholar
  26. 26.
    Tang, M. X., Redemann, C. T., and Szoka, F. C. (1996) In vitro gene delivery by degraded polyamidoamine dendrimers. Bioconj. Chem. 7, 703–714.Google Scholar
  27. 27.
    Bielinska, A., Kukowska-Latallo, J. F., Johnson, J., Tomalia, D. A., and Baker, J. R. (1996) Regulation of in vitro gene expression using; antisense oligonucle-otides or antisense expression plasmids transfected using starburst PAMAM dendrimers. Nucl. Acids Res. 24(11), 2176–2182.PubMedGoogle Scholar
  28. 28.
    Haensler, J. and Szoka, F. C. (1993) Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. Bioconj. Chem. 4(5), 372–379.Google Scholar
  29. 29.
    Kato, T., Iwamoto, K., Ando, H., Asakawa, N., Tanaka, I., Kikuchi, J., and Murakami, Y. (1996) Synthetic cationic amphiphile for liposome-mediated DNA transfection with less cytotoxicity. Biol. Pharmaceut. Bull. 19(6), 860–863.Google Scholar
  30. 30.
    Legendre, J. Y., Trzeciak, A., Bohrmann, B., Deuschle, U., Kitas, E., and Supersaxo, A. (1997) Dioleoylmelittin as a novel serum-insensitive reagent for efficient transfection of mammalian cells. Bioconj. Chem. 8(1), 57–63.Google Scholar
  31. 31.
    Hong, K., Zheng, W., Baker, A., and Papahadjopoulos, D. (1997) Stabilization of cationic liposome-plasmid DNA complexes by polyamines and poly(ethylene glycol)-phospholipid conjugates for efficient in vivo gene delivery. FEBS Lett. 400(2), 233–237.PubMedGoogle Scholar
  32. 32.
    Felgner, P. L. (1997) Nonviral strategies for gene therapy. Scientific Am. 276(6), 102–106.Google Scholar
  33. 33.
    Wong, F. M. P., Reimer, D. L., and Bally, M. B. (1996) Cationic lipid binding to DNA: characterization of complex formation. Biochemistry 35, 5756–5763.PubMedGoogle Scholar
  34. 34.
    Canonico, A. E., Conary, J. T., Meyrick, B. O., and Brigham, K. L. (1994) Aerosol and intravenous transfection of human alpha-1 antitrypsin gene to lungs of rabbits. Am. J. Resp. Cell Mol. Biol. 10(1), 24–29.Google Scholar
  35. 35.
    Leibiger, I., Leibiger, B., Sarrach, D., Walter, R., and Zuhlke, H. (1990) Genetic manipulation of rat hepatocytes in vivo. Implications for a therapy model of type-1 diabetes. Biomed. Biochim. Acta 49(12), 1193–1200.PubMedGoogle Scholar
  36. 36.
    Thierry, A. R., Lunardi-Iskandar, Y., Bryant, J. L., Rabinovich, P., Gallo, R. C., and Mahan, L. C. (1996) Systemic gene therapy: biodistribution and long-term expression of a transgene in mice. Proc. Natl. Acad Sci. USA 92, 9742–9746.Google Scholar
  37. 37.
    Schmid, R. M., Weidenbach, H., Draenert, G. F, Lerch, M. M., Liptay, S., Schorr J., Beckh, K. H., and Adler, G. (1994) Liposome-mediated in vivo gene transfer into different tissues of the gastrointestinal tract. Z. Gastroenterol. 32(12), 665–670.PubMedGoogle Scholar
  38. 38.
    Lesoon-Wood, L. A., Kirn, W. H., Kleinman, H. K., Weintraub, B. D., and Mixson, A. J. (1995) Systemic gene therapy with p53 reduces growth and metastases of a malignant human breast cancer in nude mice. Hum. Gene Ther. 6, 395–405.PubMedGoogle Scholar
  39. 39.
    Lew, D., Parker, S. E., Latimer, T., Abai, A. M., Kuwahara-Rundell, A., Doh, S. G., Yang, Z.-Y., Laface, D., Gromkowski, S. H., Nabel, G. J., Manthrope, M., and Norman, J. (1995) Cancer gene therapy using plasmid DNA: pharmacokinetic study of DNA fallowing injection in mice. Hum. Gene Ther. 6, 553–564.PubMedGoogle Scholar
  40. 40.
    Xing, X., Matin, A., Yu, D., Xia, W., Sorgi, F., Huang, L., and Hung, M. C. (1996) Mutant SV40 large T antigen as a therapeutic agent for HER-2/neu-overexpressing ovarian cancer. Cancer Gene Ther. 3(3), 168–174.PubMedGoogle Scholar
  41. 41.
    Yu, D., Matin, A., Xia, W., Sorgi, F., Huang, L., and Hung, M. C. (1995) Liposome-mediated in vivo gene transfer suppressed dissemination of ovarian cancer cells that overexpress HER-2/neu. Oncogene 11(7), 1383–1388.PubMedGoogle Scholar
  42. 42.
    Meyer, K. B., Thompson, M. M., Levy, M. Y., Barron, L. G., and Szoka, F. C. (1995) Intratracheal gene delivery to the mouse airway: characterization of plas-mid DNA expression and pharmacokinetics. Gene Ther. 2, 450–460.PubMedGoogle Scholar
  43. 43.
    McLachlan, G., Ho, L. P., Davidson-Smith, H., Samways, J., Davidson, H., Stevenson, B. J., Cathothers, A. D., Alton, E. W., Middleton, P. G., Smith, S. N., Kallmeyer, G., Michaelis, U., Seeber, S., Nanjoks, K., Greening, A. P., Innes, J. A., Oorin, J. R., and Porteous, D. J. (1996) Laboratory and clinical studies in support of cystic fibrosis gene therapy using pCMV-CFTR-DOTAP. Gene Ther. 3(12), 1113–1123.PubMedGoogle Scholar
  44. 44.
    Hyde, S. C., Gill, D. R., Higgins, C. F., Trezise, A. E., MacVinish, L. J., Cutherbert, A. W., Ratcliff, R., Evans, M. J., and Colledge, W. H. (1993) Correction of the ion transport defect in cystic fibrosis transgenic mice by gene therapy. Nature 362(6417), 250–255.PubMedGoogle Scholar
  45. 45.
    Jones, S. E., McHugh, J. D., Jomary, C., Shallal, A., and Neal, M. J. (1994) Assessment of liposomal transfection of ocular tissues in vivo. Gene Ther. 1(Suppl. 1), S61.PubMedGoogle Scholar
  46. 46.
    Parker, S. E., Khatibi, S., Margalith, M., Anderson, D., Yankauckas, M., Gromkowski, S. H., Latimer, T., Lew, D., Marquet M., Manthorpe M., Hobart, P., Hersh, E., Stopeck, A. T., and Norman, J. (1996) PlasmidDNA gene therapy: studies with the human interleukin-2 gene in tumor cells in vitro and in the murine B16 melanoma model in vivo. Cancer Gene Ther. 3(3), 175–185.PubMedGoogle Scholar
  47. 47.
    Egilmez, N. K., Cuenca, R., Yokota, S. J., Sorgi, F., and Bankert, R. B. (1996) In vivo cytokine gene therapy of human tumor xenografts in SCII) mice by liposome-mediated gene therapy. Gene Ther. 3(7), 607–614.PubMedGoogle Scholar
  48. 48.
    Nabel, G. J., Gordon, D., Bishop, D. K., Nickoloff, B. J., Yang, Z. Y., Aruga, A., Cameron, M. J., Nabel, E. G., and Chang, A. E. (1996) Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA-liposome complexes. Proc. Natl. Acad. Sci. USA 93(26), 15,388–15,393.PubMedGoogle Scholar
  49. 49.
    Hickman, M. A., Malone, R. W., Lehmann-Bruinsma, K., Sih, T. R., Knoell, D., Szoka, F. C., Walzem, R., Carlson, D. M., and Powell, J. S. (1994) Gene expression following direct injection of DNA into the liver. Hum. Gene Ther. 5(12), 1477–1483.PubMedGoogle Scholar
  50. 50.
    Caplen, N. J., Alton, E. W., Middleton, P. G., Dorin, J. R., Stevenson, B. J., Gao, X., Durham, S. R., Jeffery, P. K., Hodson, M. E., Coutelle, C., Huang, L., Porteous, D. J., Williamson, R., and Geddes, D. M. (1995) Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nat. Med. 1(1), 39–46.PubMedGoogle Scholar
  51. 51.
    Felgner, P. L., Tsai, Y. J., Sukhu, L., Wheeler, C. J., Manthorpe, M., Marshall, J., and Cheng, S. H. (1995) Improved cationic lipid formulations for in vivo gene therapy. Ann. NY Ac ad. Sci. 772, 126–139.Google Scholar
  52. 52.
    Felgner, J. H., Kumar, R., Sridhar, C. N., Wheeler, C. J., Tsai, Y. J., Border, R., Ramsey, P., Martin, M., and Felgner, P. L. (1994) Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations. J. Biol. Chem. 269(4), 2550–2561.PubMedGoogle Scholar
  53. 53.
    Balasubramaniam, R. P., Bennett, M. J., Aberle, A. M., Malone, J. G., Nantz, M. H., and Malone, R. W. (1996) Structural and functional analysis of cationic trans-fection lipids: the hydrophobic domain. Gene Ther. 3(2), 163–172.PubMedGoogle Scholar
  54. 54.
    Wheeler, C. J., Sukbu L., Yang G., Tsai Y., Bustamente C., Felgner P. L., Norman, J., and Manthorpe, M. (1996) Converting an alcohol to an amine in a cationic lipid dramatically alters the co-lipid requirement, cellular transfection activity and the ultrastructure of DNA-cytofectm complexes. Biochim. Biophys. Acta 1280, 1–11.PubMedGoogle Scholar
  55. 55.
    Farhood, H., Serbina, N., and Huang, L. (1995) The role of dioleoyl phosphati-dylethanolamine in cationic liposome mediated gene transfer. Biochim. Biophys. Acta 1235, 289–295.PubMedGoogle Scholar
  56. 56.
    Wasan, E. K., Reimer, D. L., and Bally, M. B. (1996) Plasmid DNA is protected against ultrasonic cavitation-induced damage when complexed to cationic lipo-somes. J. Pharm. Sci. 85(4), 427–433.PubMedGoogle Scholar
  57. 57.
    Wu, G. Y. and Wu, C. H. (1988) Evidence for targeted gene delivery to Hep G2 hepatoma cells in vivo. Biochemistry 27(3), 887–892.PubMedGoogle Scholar
  58. 58.
    Wu, G. Y. and Wu, C. H. (1988) Receptor-mediated gene delivery and expression in vivo. J. Biol. Chem. 263(29), 14,621–14,624.PubMedGoogle Scholar
  59. 59.
    Wagner, E., Cotten, M., Foisner, R., and Birnstiel, M. L. (1991) Transferrin-polycation-DNA complexes: the effect of polylysine on the structure of the complex and DNA delivery to cells. Proc. Natl. Acad. Sci. USA 88(10), 4255–4259.PubMedGoogle Scholar
  60. 60.
    Okada, N., Miyamoto, H., Yoshioka, T., Sakamoto, K., Katsume, A., Saito, H., Nakagawa, S., Ohsugi, Y., and Mayumi, T. (1997) Immunological studies of SK2 hybridoma cells microencapsulated with alginate-poly(L-lysine)-alginate (APA) membrane following allogenic transplantation. Biochem. Biophys. Res. Comm. 230(3), 524–527.PubMedGoogle Scholar
  61. 61.
    Liu, H. W., Ofosu, F. A., and Chang, P. L. (1993) Expression of human factor IX by microencapsulated recombinant fibroblasts. Hum. Gene Ther. 4(3), 291–301.PubMedGoogle Scholar
  62. 62.
    Halle, J. P., Bourassa, S., Leblond, F. A., Chevalier, S., Beudry, M., Chapdelaine, A., Cousineau, S., Saintonge, J., and Yale, J. F. (1993) Protection of islets of Langerhans from antibodies by microencapsulation with alginate-poly-L-lysine membranes. Transplantation 55(2), 350–354.PubMedGoogle Scholar
  63. 63.
    Tomalia, D. A., Naylor, A. M., and Goddard, W. A. (1990) Starburst dendrimers: molecular-level control of size, shape surface chemistry, topology, and flexibility from atoms to macroscopic matter. Angew. Chem. Int. Ed. Engl. 29, 138–175.Google Scholar
  64. 64.
    Tomalia, D. A. and Durst, H. D. (1993) Genealogically directed synthesis: starburst/cascade dendrimers and hyperbranched structures. Top. Curr. Chem. 165, 193–313.Google Scholar
  65. 65.
    Legendre, J.-Y. and Szoka, F. C. (1993) Cyclic arnphipathic peptide-DNA complexes mediate high efficiency transfection of adherent mammalian cells. Proc. Natl. AcadSci. USA 90, 893–897.Google Scholar
  66. 66.
    Ohmori, N., Niidome, T., Wada, A., Hirayama, T., Hatakeyama, T., and Aoyagi, H. (1997) The enhancing effect of anionic alpha-helical peptide on cationic pep-tide-mediating transfection systems. Biochem. Biophys. Res. Comm. 235(3), 726–729.PubMedGoogle Scholar
  67. 67.
    Buschle, M., Cotten, M., Kirlappos, H., Mechtler, K., Shaffner, G., Zauner, W., Birnstiel, M. C., and Wagner, E. (1995) Receptor-mediated gene transfer into human T lymphocytes via binding of DNA/CD3 antibody particles to the CD3 T cell receptor. Hum. Gene Ther. 6(6), 753–761.PubMedGoogle Scholar
  68. 68.
    Merwin, J. R., Noell G. S., Thomas, W. L., Chiou, H. C., DeRome, M. E., McKee, T. D., Spitalny, G. L., and Findeis, M. A. (1994) Targeted delivery of DNA using; YEE(GalNAcAH)3, a synthetic glycopeptide ligand for the asialoglycoprotein receptor. Bioconj. Chem. 5(6), 612–620.Google Scholar
  69. 69.
    McKee, T. D., DeRome, M. E., Wu, G. Y., and Findeis, M. A. (1994) Preparation of asialoorosomucoid-polylysine conjugates. Bioconj. Chem. 5(4), 306–311.Google Scholar
  70. 70.
    Stankovics, J., Crane, A. M., Andrews, E., Wu, C. H., Wu, G. Y., and Ledley, F. D. (1994) Overexpression of human methylmalonyl CoA mutase in mice after in vivo gene transfer with asialoglycoprotein/polylysine/DNA complexes. Hum. Gene Ther. 5(9), 1095–1104.PubMedGoogle Scholar
  71. 71.
    Ferkol, T., Pellicena-Palle, A., Eckrnan, E., Perales, J. C., Trzaska, T., Tosi, M., Redline, R., and Davis, P. B. (1996) Immunologic responses to gene transfer into mice via the polymeric immunoglobulin receptor. Gene Ther. 3(8), 669–678.PubMedGoogle Scholar
  72. 72.
    Phillips, S. C. (1995) Receptor-mediated DNA delivery approaches to human gene therapy. Biologicals 23(1), 13–16.PubMedGoogle Scholar
  73. 73.
    Lozier, J. N., Thompson, A. R., Hu, P. C., Read, M., Brinkhous, K. M., High, K. A., and Curiel, D. T. (1994) Efficient transfection of primary cells in a canine hemophilia B model using adenoviruspolylysine-DNA complexes. Hum. Gene Ther. 5(3), 313–322.PubMedGoogle Scholar
  74. 74.
    Cristiano, R. J., Smith, L. C., Kay, M. A., Brinkely, B. R., and Woo, S. L. (1993) Hepatic gene therapy: efficient gene delivery and expression in primary hepato-cytes utilizing a conjugated adenovirus-DNA complex. Proc. Natl. Acad. Sci. USA 90(24), 11,548–11,552.PubMedGoogle Scholar
  75. 75.
    Cristiano, R. J., Smith, L. C., and Woo, S. L. (1993) Hepatic gene therapy: aden-ovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes. Proc. Natl. Acad. Sci USA 90(6), 2122–2126.PubMedGoogle Scholar
  76. 76.
    Plank, C., Katloukal, K., Cotten, M., Mechtler, K., and Wagner, E. (1992) Gene transfer into hepatocytes using asialoglycoprotein receptor mediated endocylosis of DNA complexed with an artificial tetra-antennary galactose ligand. Bioconj. Chem. 3, 533–539.Google Scholar
  77. 77.
    Wagner, E., Plank, C., Katloukal, K., Cotten, M., and Birnstie, M. L. (1992) Influenza virus hemagglutinin HA-2 terminal fusogenic peptides augment gene transfer by transferrinpolylysine-DNA complexes: toward a synthetic virus-like gen∼e transfer vehicle. Proc. Natl. Acad. Sci. USA 89(17), 7934–793.PubMedGoogle Scholar
  78. 78.
    Fritz, J. D., Herweijer, H., Zhang, G., and Wolff, J. A. (1996) Gene transfer into mammalian cells using his/one-condensed plasmid DNA. Hum. Gene Ther. 7(12), 1395–1404.PubMedGoogle Scholar
  79. 79.
    Papahadjopoulos, D., Hong, K., Kirpotin, D., Zheng, W., Shao, V., Park, J., and Benz, C. (1997) Ligand-directed targeting of liposomes in vivo: formulations for delivery of drugs and genes to tumors. Control. Rel. Bioact. Mater. 24, 159,160.Google Scholar
  80. 80.
    Sambrook, J., Fritsch, E. F., and Maniatis, T., eds. (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  81. 81.
    Ausubel, F. M., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A., and Struhl, K., eds. (1997) Protocols in Molecular Biology. Wiley, Boston, MA.Google Scholar
  82. 82.
    Haugland, R. P. (1996) Handbook of Fluorescent Probes and Research Chemicals (Spence, T. Z., ed.), Molecular Probes, Eugene, OR.Google Scholar
  83. 83.
    Hofland, H. E., Shephard, L., and Sullivan, S. M. (1996) Formation of stable cationic lipid/DNA complexes for gene transfer. Proc. Natl. Acad. Sci. USA 93(14), 7305–7309.PubMedGoogle Scholar
  84. 84.
    Thurnher, M., Wagner, E., Clause, n H., Mechtler, K., Rusconi, S., Dinter, A., Birstiel, M. L., Berger, E. G., and Cotten, M. (1994) Carbohydrate receptor-mediated gene transfer to human T leukaemic cells. Glycobiol. 4(4), 429–435.Google Scholar
  85. 85.
    Erbacher, P., Bousser, M. T., Raimond, J., Monsigny, M., Midoux, P., and Roche, A. C. (1996) Gene transfer by DNA/glycosylated polylysine complexes into human blood monocyte-derived macrophages. Hum. Gene Ther. 7(6), 721–729.PubMedGoogle Scholar
  86. 86.
    Holt, C., Parker, T. G., and Dalgleish, D. G. (1975) Measurement of particle sizes by elastic and quasi-elastic light scattering. Biochim. Biaphys. Acta 400(2), 283–292.Google Scholar
  87. 87.
    Pecora, R. (1972) Quasi-elastic light scattering from macromolecules. Ann. Rev. Biophys. Bioeng. 1, 257–276.Google Scholar
  88. 88.
    Sternberg, B., Sorgi, F. L., and Huang, L. (1994) New structwres in complex formation between DNA and cationic liposomes visualized by fireeze-fracture electron microscopy. FEBS Lett. 356, 361–366.PubMedGoogle Scholar
  89. 89.
    Radler, J. O., Koltover, I., Salditt, T., and Safinya, C. R. (1997) Structure of DNA-cationic liposome complexes: DNA intercalation in multilarnellar membranes in distinct interhelical packing regimes. Science 275, 810–814.PubMedGoogle Scholar
  90. 90.
    Hui, S. W., Langner, M., Zhao, Y. L., Ross, P., Hurley, E., and Chan, K. (1996) The role of helper lipids in cationic liposome-mediated gene transfer. Biophys. J. 71, 590–599.PubMedGoogle Scholar
  91. 91.
    Gustafsson, J., Arvidson, G., Karlsson, G., and Almgren, M. (1995) Complexes between cationic liposomes and DNA visualized by cryo-TEM. Biochim. Biophys. Acta 1235(2), 305–312.PubMedGoogle Scholar
  92. 92.
    Dubochet, J., Adrian, M., Chang, J. J., Homo, J. C., Lepault, J., McDowall, A. W., and Schultz, P. (1988) Cryo-electron microscopy of vitrified specimens. Q. Rev. Biophys. 21, 129–288.PubMedGoogle Scholar
  93. 93.
    Bellare, J. R., Davis, H. T., Scrivep, L. E., and Talmon, Y. (1988) Controlled environment vitrification system (CEVS): an improved sample preparation technique. J. Electron Miscrosc. Tech. 10, 87–111.Google Scholar
  94. 94.
    Bally, M. B., Zhang, Y.-P., Wong, F. M. P., Kong, S., Wasan, E., and Reimer, D. L. (1997) Lipid/DNA complexes as an intermediate in the preparation of particles for gene transfer: an alternative to cationic liposome/DNA aggregates. Adv. Drug Deliv. Rev. 24, 275–290.Google Scholar
  95. 95.
    Struck, D. K., Hoekstra, D., and Pagano, R. E. (1981) Use of resonance energy transfer to monitor membrane fusion. Biochemistry 20, 4093–4099.PubMedGoogle Scholar
  96. 96.
    Fung, B. K. K. and Stryer, L. (1978) Surface density determination by fluorescence energy transfer. Biochemistry 17(24), 5241–5248.PubMedGoogle Scholar
  97. 97.
    Stryer, L. (1978) Fluorescence energy transfer as a spectroscopic ruler. Ann. Rev. Biochem. 47, 819–832.PubMedGoogle Scholar
  98. 98.
    Holland, J. W., Hui, C., Cullis, P. R., and Madden, T. D. (1996) Poly(ethylene gly-col)-lipid conjugates regulate the calcium-induced fusion of liposomes composed of phosphatidylethanolamine and phosphatidylserine. Biochemistry 35(8), 2618–2624.PubMedGoogle Scholar
  99. 99.
    Duzgunes, N., Nir, S., Wilshut, J., Bentz, J., Newton, C., Portis, A., and Papahadjopoulos, D. (1981) Calcium-and magnesium-induced fusion of mixed phosphatidylserine/phosphatidylcholine vesicles: effect of ion binding. J. Membr.Biol. 59, 115–125.PubMedGoogle Scholar
  100. 100.
    Stamatatos, L., Leventis, R., Zuckermann, M. J., and Silvius, J. R. (1988) Interactions of cationic lipid vesicles with negatively charged phospholipid vesicles and biological membranes. Biochemistry 27(11), 3917–3925.PubMedGoogle Scholar
  101. 101.
    Wasan, E. K., Fairchild, A., and Bally, M. B. (1997) Cationic liposome-plasmid DNA complexes used for gene transfer retain a significant trapped volume. J. Pharm. Sci. 87(1), 9–14.Google Scholar
  102. 102.
    Xu, Y. and Szoka, F. C. (1996) Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 35, 5616–5623.PubMedGoogle Scholar
  103. 103.
    Harvie, P., Wong, F. M. P., Reimer, D. L., and Bally, M. B. (1998) Self-assembling lipid-DNA particles: anionic membrane-mediated dissociation. Biophys. J. 47(10), 1611–1617.Google Scholar
  104. 104.
    Schott, H. (1969) Hydrophile-lipophile balance and cloud points of nonionic surfactants. J. Pharm. Sci. 58(12), 1443–1449.PubMedGoogle Scholar
  105. 105.
    Smolarsky, M., Teitelbaum, D., Sela, M., and Gitler, C. (1977) A simple fluorescent method to determine complement mediated liposome immune lysis. Immunol. Meth. 15, 255–265.Google Scholar
  106. 106.
    Ellens, H., Bentz, J., and Szoka, F. C. (1984) pH-induced destabilization of phos-phatidylethanolamine-containing liposomes: role of bilayer contact. Biochemistry 23, 1532–1538.PubMedGoogle Scholar
  107. 107.
    Wilschut, J. and Papahadjopoulos, D. (1979) Ca2+-induced fusion of phospholipid vesicles monitored by mixing of aqueous contents. Nature 281, 691,692.Google Scholar
  108. 108.
    Bailey, A. L. and Cullis, P. R. (1997) Membrane fusion with cationic lipo-somes: effects of target membrane lipid composition. Biochemistry 36(7), 1628–1634.PubMedGoogle Scholar
  109. 109.
    Arscott, P. G., Li, A. Z., and Bloomfield, V. A. (1990) Condensation of DNAby trivalent cations. 1. Effects of DNA length and topology on the size and shape of condensed particles. Biopolymers 30, 619–630.PubMedGoogle Scholar
  110. 110.
    Plum, G. E., Arscott, P. G., and Bloomfield, V. A. (1990) Condensation of DNA by trivalent cations. 2. Effects of cation structure. Biopolymers 30, 631–643.PubMedGoogle Scholar
  111. 111.
    Blumfield, V. A. (1991) Condensation of DNAby multivalent cations: considerations on mechanism. Biopolymers 31, 1471–1481.Google Scholar
  112. 112.
    Thierry, A. R., Rabinovich, P., Peng, B., Mahan, L. C., Bryant, J. L., and Gallo, R. C. (1997) Characterization of liposome-mediated gene delivery: expression, stability and pharmacokinetics of plasmid DNA. Gene Ther. 4(3), 226–237.PubMedGoogle Scholar
  113. 113.
    Bligh, E. G. and Dyer, W. J. (1959) A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37(8), 911–917.PubMedGoogle Scholar
  114. 114.
    Lewis, J. G., Lin, K. Y., Kothvale, A., Flanagan, W. M., Matteucci, M. D., DePrince, R. B., Mook, R. A., Jr., Hendren, R. W., and Wagner, R. W. (1996) A serum-resistant cytofectin for cellular delivery of antisense oligodeoxy-nucleotides and plasmid DNA. Proc. Natl. Acad. Sci. USA 93(8), 3176–3181.PubMedGoogle Scholar
  115. 115.
    Zabner, J., Fasbender, A. J., Moninger, T., Poellinger, K. A., and Welsh, M. J. (1995) Cellular and molecular barriers to gene transfer by a cationic lipid. J. Biol. Chem. 270(32), 18,997–19,007.PubMedGoogle Scholar
  116. 116.
    Lasic, D. D. and Templeton, N. S. (1996) Liposomes in gene therapy. Adv. Drug Del. Rev. 20(2-3), 221–266.Google Scholar
  117. 117.
    Hart, S. L., Harbottle, R. P., Cooner, R., Miller, A., Williamson, R., and Coutelle, C. (1995) Gene delivery and expression mediated by an integrin-binding pep-tide. Gene Ther. 2(8), 552–554.PubMedGoogle Scholar
  118. 118.
    Hara, T., Liu, F., Liu, D., and Huang, L. (1997) Emulsion formulations as a vector for gene delivery in vitro and in vivo. Adv. Drug Del. Rev. 24, 265–271.Google Scholar
  119. 119.
    Reimer, D. L., Kong, S., and Bally, M. E. (1997) Analysis of cationic liposome-mediated interactions of plasmid DNA with murine and human melanoma cells in vitro. J. Biol. Chem. 272(31), 19,480–19,487.PubMedGoogle Scholar
  120. 120.
    Hirt, B. (1967) Selective extraction of polyoma DNA from infected mouse cell cultures. J. Mol. Biol. 26(2), 365–369.PubMedGoogle Scholar
  121. 121.
    Kawabata, K., Takakura, Y., and Hashida, M. (1995) The fate of plasmid DNA after intravenous injection in mice-involvement of scavenger receptors in its hepatic uptake. Pharm. Res. 12(6), 825–830.PubMedGoogle Scholar
  122. 122.
    Osaka, G., Carey, K., Cuthbertson, A., Godowski, P., Patapoff, T., Ryan, A., Gadek, T., and Mordenti, J. (1996) 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. J. Pharm. Sci. 85(6), 612–618.PubMedGoogle Scholar
  123. 123.
    Nomura, T., Nakahima, S., Kawabata, K., Yamashita, F., Takakura, Y., and Hashida, M. (1997) Intratumoral pharmacokinetics and in vivo gene expression of naked plasmid DNA and its cationic liposome complexes after direct gene transfer. Cancer Res. 57(13), 2681–2686.PubMedGoogle Scholar
  124. 124.
    Reimer, D. L., Kong, S., Monk, M., Tan, P., Wasan, E., and Bally, M. B. (1997) Factors influencing in vivo liposome-mediated transfection of B 16/ BL6 melanoma tumor models: a pharmacodynamic study. J. Pharmacol. Exp. Ther. JPET 289(2), 807–815.Google Scholar
  125. 125.
    Levy, M. Y., Barron, L. G., Meyer, K. B., and Szoka, F. C. (1996) Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood. Gene Ther. 3, 201–211.PubMedGoogle Scholar
  126. 126.
    Winegar, R. A., Monforte, J. A., Suing, K. D., Oloughlin, K. G., Rudd, C. J., and Macgregor, J. T. (1996) Determination of tissue distribution of an intramuscular plasmid vaccine using PCR and in situ DNA hybridization. Hum. Gene Ther. 7(17), 2185–2194.PubMedGoogle Scholar
  127. 127.
    Porcher, C., Malinge, M. C., Picat, C., and Grandchamp, B. (1992) A simplified method for determination of specif∼c DNA or RNA copy number using quantitative PCR and an automatic DNA sequencer. Biotechnology 13(1), 106–114.Google Scholar
  128. 128.
    Sperisen, P., Wang, S. M., Reichenbach, P., and Nabholz, M. (1992) A PCR-based assay for reporter gene expression. PCR Meth. Appl. 1(3), 164–170.Google Scholar
  129. 129.
    Friend, D. S., Papahadjopoulos, D., and Debs, R. J. (1996) Endocytosis and intracellular processing accompanying transfection mediated by cationic lipo-somes. Biochim. Biophys. Acta 1278(1), 41–50.PubMedGoogle Scholar
  130. 130.
    Schwedener, R. A., Trub, T., Schott, H., Langhals, H., Barth, R. F., Groscurth, P., and Hengartner, H. (1990) Comparative studies of the preparation of immunoliposomes with the use of two bifunctional coupling agents and investigation of in vitro immunoliposome-target cell binding by cytofluorometry and electron microscopy. Biochim. Biophys. Acta 1026(1), 69–79.Google Scholar
  131. 131.
    Flasher, D., Konopka, K., Chamow, S. M., Dazin, P., Ashkenazi, A., Pretzer, F. (1994) Liposome targeting to immune deficiency virus type 1-infected cells via recombinant soluble CD4 and CD4 immunoadhesin (CD4-IgG). Biochim. Biophys. Acta 1194(1), 185–196.PubMedGoogle Scholar
  132. 132.
    Bally, M. B., May, L. D., Hope, M. J., and Nayar, R. (1993) Pharrnacodynamics of liposomal drug carriers: methodological considerations, in Liposome Technology (Gregoriadis, G., ed.), CRC, Boca Raton, FL, pp. 27–41.Google Scholar
  133. 133.
    Parker, S. E., Ducharme, D., Norman, J., and Wheeler, C. J. (1997) Tissue distribution of the cytofectin component of a plasmid DNA/cationic lipid complex following intravenous administration in mice. Hum. Gene Ther. 8(4), 393–401.PubMedGoogle Scholar
  134. 134.
    Cowan, P. J., Shinkel, T. A., Witort, E. J., Barlow, H., Pearse, M. J., and d’Apice, A. J. (1996) Targeting gene expression to endothelial cells in transgenic mice using the human intercellular adhesion molecule 2 promoter. Transplantation 62(2), 155–160.Google Scholar
  135. 135.
    Vile, R. G. and Hart, I. R. (1994) Targeting of cytokine gene expression to malignant melanoma cells using tissue-specific promoter sequences. Ann. Oncol. 5(Suppl. 4), 59–65.PubMedGoogle Scholar
  136. 136.
    Gerloni, M., Billetta, R., Xiong, S. D., and Zanetti, M. (1997) Somatic transgene immunization with DNA encoding an irnmunoglobulin heavy chain. DNA Cell Biol. 16(5), 611–625.PubMedGoogle Scholar
  137. 137.
    Liang, X., Hartikka, J., Sukhu, L., Manthorpe, M., and Hobart, P. (1996) Novel, high expressing and antibiotic-controlled plasmid vectors designed for use in gene therapy. Gene Ther. 3(4), 350–356.PubMedGoogle Scholar
  138. 138.
    Fishman, G. I., Kaplan, M. L., and Buttrick, P. M. (1994) Tetracycline-regulated cardiac gene expression in vivo. J. Clin. Invest. 93(4), 1864–1868.PubMedGoogle Scholar
  139. 139.
    Delort, J. P. and Capecchi, M. R. (1996) TAXI/WAS-a molecular switch to control expression of genes in vivo. Hum. Gene Ther. 7(7), 809–820.PubMedGoogle Scholar
  140. 140.
    Hallahan, D. E., Mauceri, H. J., Seung, L. P., Dunphy, E. J., Wayne, J. D., Hanna, N. N., Toledano, A., Hellman, S., Kufe, D. W., and Weichselbaum, R. R. (1995) Spatial and temporal control of gene therapy using ionizing radiation. Nature Med. 1(8), 786–791.PubMedGoogle Scholar
  141. 141.
    Mount, R. C., Jordan, B. E., and Hadfield, C. (1996) Reporter gene systems for assaying gene expression in yeast. Meth. Mol. Biol. 53, 239–248.Google Scholar
  142. 142.
    Cui, C., Wani, M. A., Wight, D., Kopchick, J., and Stambrook, P. J. (1994) Reporter genes in transgenic mice. Transgen. Res. 3(3), 182–194.Google Scholar
  143. 143.
    Mittal, S. K., Bett, A. J., Prevec, L., and Graham, F. L. (1995) Foreign gene expression by human adenovirus type 5-based vectors studies using firefly luciferase and bacterial beta-galactosidase gene as reporters. Virology 210(1), 226–230.PubMedGoogle Scholar
  144. 144.
    Hanna, Z., Fregeau, C., Prefontaine, G., and Brousseau, R. (1984) Construction of a family of universal expression plasmid vectors. Gene 30, 247–250.PubMedGoogle Scholar
  145. 145.
    Shen Q., van Beusechem, V. W., Einerhand, M. P., Hendrikx, P. J., and Valerio, D. (1991) Construction and expression of an adenosine deaminase:lacZ fusion gene. Gene 98(2), 283–287.PubMedGoogle Scholar
  146. 146.
    Srienc, F., Campbell, J. L., and Bailey, J. E. (1986) Flow cytometry analysis of recombinant Saccharomyces cerevisiae populations. Cytometry 7(2), 132–141.PubMedGoogle Scholar
  147. 147.
    Lal, B., Cahan, M. A., Couraud, P. O., Goldstein, G. W., and Laterra, J. (1994) Development of endogenous beta-galactosidase and autofluorescence in rat brain microvessels: implications for cell tracking and gene transfer studies. J. Histochem. Cytochem. 42(7), 953–956.PubMedGoogle Scholar
  148. 148.
    Jiao, S., Acsadi, G., Jani, A., Felgner, P. L., and Wolff, J. A. (1992) Persistence of plasmid DNA and expression in rat brain cells in vivo. Exper. Neurol. 15(3), 400–413.Google Scholar
  149. 149.
    Yoshimura, K., Rosenfeld, M. A., Nakamura, H., Scherer, E. M., Pavirani, A., Lecocq, J. P., and Crystal, R. G. (1992) Expression of the human cystic fibrosis transmembrane conductance regulator gene in the mouse lung after in vivo intratracheal plasmid-mediated gene transfer. Nucl. Acids Res. 20(12), 3233–3240.PubMedGoogle Scholar
  150. 150.
    Jiao, S., Williams, P., Berg, R. K., Hodgeman, B. A., Liu, L., Repetto, G., and Wolff, J. A. (1992) Direct gene transfer into nonhuman primate myofibers in vivo. Hum. Gene Ther. 3(1), 21–33.PubMedGoogle Scholar
  151. 151.
    Gorman, C. M., Moffat, L. F., and Howard, B. H. (1982) Recombinant genomes which express chloramphenicol acetyltransferase in mammarlian cells. Mol. Cell Biol. 2(9), 1044–1051.PubMedGoogle Scholar
  152. 152.
    Sleigh, M. J. (1986) A nonchromatographic assay for expression of the chloramphenicol acetyltransferase gene in eukaryotic cells. Anal. Biochem. 156(1), 251–256.PubMedGoogle Scholar
  153. 153.
    de Wet, J. R., Wood, K. V., Helinski, D. R., and DeLuca, M. (1985) Cloning of firefly luciferase cDNA and the expression of active luciferase in Escherichia. coli. Proc. Natl. Acad. Sci. USA 82(23), 7870–7873.PubMedGoogle Scholar
  154. 154.
    Chapman, G. D., Lim, C. S., Gammon, R. S., Culp, S. C., Desper, J. S., Bauman, R. P., Swain, J. L., and Stack, R. S. (1992) Gene transfer into coronary arteries of intact animals with a percutaneous balloon-catheter. Circ. Res. 71(1), 27–33.PubMedGoogle Scholar
  155. 155.
    de Wet, J. R., Wood, K. V., DeLuca, M., Helinski, D. R., and Subramani, S. (1987) Firefly luciferase gene: structure and expression in mammalian cells. Mol. Cell Biol. 7(2), 725–737.PubMedGoogle Scholar
  156. 156.
    Brasier, A. R., Tate, J. E., and Habener, J. F. (1989) Optimized use of firefly luciferase assay as a reporter gene in mammalian tell lines. Biotechnology 7(10), 1116–1122.Google Scholar
  157. 157.
    Kricka, L. J. (1991) Chemiluminescence and bioluminescence. Clin. Chem. 37(9), 1472–1481.PubMedGoogle Scholar
  158. 158.
    Fasbender, A., Marshall, J., Moninger, T. O., Grunst, T., Cheng, S., and Welsh, M. J. (1997) Effect of co-lipids in enhancing cationic lipid-medialed gene transfer in vitro and in vivo. Gene Ther. 4, 716–725.PubMedGoogle Scholar
  159. 159.
    Marquet, M., Horn, N. A., and Meek, J. A. (1995) Process development for the manufacture of plasmid DNA vectors for use in gene therapy. BioPharm. 8(7), 26–37.Google Scholar
  160. 160.
    Weber, M., Moller, K., Welzeck, M., and Schorr, J. (1995) The effects of lipopolysaccharide on transfection in eukaryotic cells. Biotechnology 19, 930–940.Google Scholar
  161. 161.
    Chang, N.-S. and Mattison, J. (1996) Rapicl separation of DNA from ethidium bromide and cesium chloride in ultracentrifugation gradients by a desalting column. Biotechnology 14(3), 342,343.Google Scholar
  162. 162.
    Davis, H. L., Schleef, M., Moritz, P., Mancini, M., Schorr, J., and Whalen, R. G. (1996) Comparison of plasmid DNA preparation methods for direct gene transfer and genetic immunization. Biotechnology 21(1), 92–99.Google Scholar
  163. 163.
    Wicks, I. P., Howell, M. L., Hancock, T., Kohsaka, H., Olee, T., and Carson, D. A. (1995) Bacterial lipopolysaccharide copurifies with plasmid DNA: implications for gene therapy. Hum. Gene Ther. 6, 317–323.PubMedGoogle Scholar
  164. 164.
    Cotten, M., Baker, A., Saltik, M., Wagner, E., and Buschle, M. (1994) Lipopolysaccharide is a frequent contaminant of plasmid DNA preparations and can be toxic to primary human cells in the presence of adenovirus. Gene Ther. 1, 239–246.PubMedGoogle Scholar
  165. 165.
    Bywater, M., Bywater, R., and Hellman, C. (1983) A novel chromatographic procedure for purification of bacterial plasmids. Anal. Biochem. 132, 219–224.PubMedGoogle Scholar
  166. 166.
    Vo-Quang, T., Malpiece, Y., Buffard, D., Kaminski, P. A., Vidal, D., and Strosberg, A. D. (1985) Rapid, large-scale purlfication of plasmid DNA by medium or low pressure gel filtration. Application: construction of thermo-amplifiable expression vectors. Biosci. Rep. 5, 101–111.PubMedGoogle Scholar
  167. 167.
    Raymond, G. J., Bryant, P. K., Nelson, A., and Johnson, J. D. (1988) Large-scale isolation of covalently closed circular DNA (cccDNA) using gel filtration chromatography. Anal. Biochem. 173, 125–133.PubMedGoogle Scholar
  168. 168.
    Weintraub, H., Cheng, P. F., and Conrad, K. (1996) Expression of transfected DNA depends on DNA topology. Cell 46, 115–122.Google Scholar
  169. 169.
    Lis, J. T. (1980) Fractionation of DNA frapments by polyethylene glycol precipitation. Meth. Enzymol. 65, 347–353.PubMedGoogle Scholar
  170. 170.
    Laws, G. M. and Adams, S. P. (1996) Measurement of 8-OHdG in DNA by HPLC-ECD: the importance of DNA purity. Biotechnology 20(1), 36–38.Google Scholar
  171. 171.
    Okamoto, T., Mitsuhashi, M., and Kikkawa, Y. (1994) Fluorometric nuclear run-on assay with oligonucleotide probe immobilized on plastic plates. Anal. Biochem. 221, 202–204.PubMedGoogle Scholar
  172. 172.
    Kichler, A., Mechtler, K., Behr, J.-P. and Wagner, E. (1997) Influence of membrane-active peptides on lipospermine/DNA complex mediated gene transfer. Bioconj. Chem. 8, 213–221.Google Scholar
  173. 173.
    Arndt-Jovin, D. J. and Jovin, T. M. (1989) Florescence labeling and microscopy of DNA. Meth. Cell Biol. 30, 417–448.Google Scholar
  174. 174.
    Szoka, F. and Papahadjopoulos, D. (1978) Procedure for preparation of lipo-somes with large internal aqueous space and high capture by reverse-phase evaporation. Proc. Natl. Acad. Sci. USA 75, 4194–4198.PubMedGoogle Scholar
  175. 175.
    Mayhew, E., Lazo, R., and Vail, W. J. (1984) Preparation of liposomes entrapping cancer chemotherapeutic agents for experimental in vivo and in vitro uses, in Liposome Technology (Gregoriadis, G., ed.), CRC, Boca Raton, FL, pp. 19–31.Google Scholar
  176. 176.
    Barenholtz, Y., Amselem, S., and Lichtenberg, D. (1979) A new method for preparation of phospholipid vesicles (liposomes)-French press. FEBS Lett. 99(1), 210–214.Google Scholar
  177. 177.
    Hope, M. J., Bally, M. B., Webb, G., and Cullis, P. R. (1985) Production of large unilamellar vesicles by a rapid extrusion procedure: characterization of size distribution, trapped volume, and ability to maintain a membrane potential. Biochim. Biophys. Acta 812, 55–65.Google Scholar
  178. 178.
    Ellens, H., Bentz, J., and Szoka, F. C. (1986) Fusion of phosphatidylethanol-amine-containing liposomes and mechanism of the La-HII phase transition. Biochemistry 25, 4141–4147.PubMedGoogle Scholar
  179. 179.
    Siegel, D. P., Green, W. J., and Talmon, Y. (1994) The mechanism of lamellar-to-inverted hexagonal phase transitions: a study using temperature-jump cryo-electron microscopy. Biophys. J. 66(2 Pt. 1), 402–414.PubMedGoogle Scholar
  180. 180.
    Harasym, T. O., Tardi, P., Longman, S. A., Ansell, S., Bally, M. B., Cullis, P. R., and Choi, L. S. (1995) Poly(ethylene glycol)-modified phospholipids prevent aggregation during covalent conjugation of proteins to liposomes. Bioconj. Chem. 6(2), 187–194.Google Scholar
  181. 181.
    Lee, R. J. and Low, P. S. (1995) Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro. Biochim. Biophys. Acta 1233(2), 134–144.PubMedGoogle Scholar
  182. 182.
    Lee, R. J. and Huang, L. (1996) Folate-targeted anionic liposome-entrapped polylysinecondensed DNA for tumor-cell specific gene transfer. J. Biol. Chem. 271(4), 8481–8487.PubMedGoogle Scholar
  183. 183.
    Thomas, W. H. and Lee, Y. K. (1994) Particles in intravenous solutions: a review. NZMed. J. 80(522), 170–178.Google Scholar
  184. 184.
    Cullis, P. R., Hope, M. J., Bally, M. B., Madden, T. D., Mayer, L. O., and Janoff, A. (1987) Liposomes as pharmaceuticals, in Liposomes: From Biophysics to Therapeutics (Ostro, M. J., ed.), Marcel Dekker, New York, pp. 39–72.Google Scholar
  185. 185.
    Abra, R. M. and Hunt, C. A. (1981) Liposome disposition in vivo. III. Dose and vesicle-size effects. Biochim. Biophys. Acta 666(3), 493–503.PubMedGoogle Scholar
  186. 186.
    Allen, T. M., Austin, G. A., Chonn, A., Lin, L., and Lee, K. C. (1991) Uptake of liposomes by cultured mouse bone marrow macrophages: influence of liposome composition and size. Biochim. Biophys. Acta 1061(1), 56–64.PubMedGoogle Scholar
  187. 187.
    Moghimi, S. M., Porter, C. J., Muir, I. S., Illum, L., and Davis, S. S. (1991) Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. Biochem. Biophys. Res. Comm. 177(2), 861–866.PubMedGoogle Scholar
  188. 188.
    Kalin, B., Sellin, P., von Krusenstierna, S., Schnell, P. O., and Jacobsson, H. (1991) Effect of size fractionation on the distribution of an albumin colloid in the reticuloendothelial system of the mouse. Intl. J. Rad Applic. Instrumen.Part B, Nucl. Med Biol. 18(7), 817–820.Google Scholar
  189. 189.
    Siegel, D. P. (1986) Inverted micellar intermediates and the transitions between lamellar, cubic and inverted hexagonal lipid phases. I. Mechanism of the La to HII phase transitions. Biophys. J. 49, 1155–1170.PubMedGoogle Scholar
  190. 190.
    Siegel, D. P. (1986) Inverted micellar intermediates and the transitions between lamellar, cubic and inverted hexagonal lipid phases. II. Implications for membrane-membrane interactions and membrane fusion. Biophys. J. 49, 1171–1183.PubMedGoogle Scholar
  191. 191.
    Boggs, J. M. (1987) Lipid intermolecular hydrogen bonding: influence on structural organization and membrane function. Biochim. Biophys. Acta 906, 353–404.PubMedGoogle Scholar
  192. 192.
    Hui, S. W., Stewart, T. P., Yeagle, P. L., and Albert, A. D. (1981) Bilayer to non-bilayer transition in mixtures of phosphatidylethanolarnine and phosphati-dylcholine: implications for membrane properties. Arch. Biochem. Biophys. 207(2), 227–240.PubMedGoogle Scholar
  193. 193.
    Stegmann, T. and Legendre, J.-Y. (1997) Gene transfer mediated by cationic lipids: lack of correlation between lipid-mixing and transfection. Biochim. Biophys. Acta 1325, 71–79.PubMedGoogle Scholar
  194. 194.
    Wolff, J. A., Ludtke, J. J., Acsadi, G., Williams, P., and Jani, A. (1992) Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet. 1(6), 363–369.PubMedGoogle Scholar
  195. 195.
    Acsadi, G., Dickson, G., Love, D. R., Jani, A., Walsh, F. S., Gurusinghe, A., Wolff, J. A., and Davies, K. E. (1991) Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature 352(6338), 815–818.PubMedGoogle Scholar
  196. 196.
    Wolff, J. A., Williams, P., Acsadi, G., Jiao, S., Jani, A., and Chong, W. (1991) Conditions affecting direct gene transfer into rodent muscle in vivo. Biotechnology 11(4), 474–485.Google Scholar
  197. 197.
    Bainton, D. (1991) The discovery of lysosomes. J. Cell Biol. 91, 66S–76S.Google Scholar
  198. 198.
    Labat-Moleur, F., Steffan, A. M., Brisson, C., Perron, H., Feugeas, O., Furstenberger, P., Oberling, F., Brambilla, E., and Behr, J. P. (1996) An electron microscopy study into the mechanism of gene transfer with lipopolyamines. Gene Ther. 3(11), 1010–1017.PubMedGoogle Scholar
  199. 199.
    Nakanishi, M., Uchida, T., and Sugawa, H. (1985) Efficient introduction of content of liposomes into cells using HVJ (Sendai virus). Exp. Cell Res. 159, 399–409.PubMedGoogle Scholar
  200. 200.
    Chen, X., Li, Y., Xie, Y., Aizicovici, S., Snodgrass, R., Wagner, T. E., and Platika, D. (1995) A novel nonviral cytoplasmic gene expression system and its implications in cancer gene therapy. Ca. Gene Ther. 2(4), 281–289.Google Scholar
  201. 201.
    Kaneda, Y., Iwai, K., and Uchida, T. (1989) Increased expression of DNA cointroduced with nuclear protein in adult rat liver. Science 243, 374–378.Google Scholar
  202. 202.
    Tomita, N., Higaki, J., Ogihara, T., Kondo, T., and Kaneda, Y. (1994) A novel gene-transfer technique mediated by HVJ (Sendai virus), nuclear protein, and liposomes. Ca. Detec. Preven. 18(6), 485–491.Google Scholar
  203. 203.
    Tartakoff, A. M. (1987) The Secretory and Endocytic Paths: Mechanism and Specificity of Vesicular Traffic in the Cell Cytoplasm. Wiley, New York.Google Scholar

Copyright information

© Humana Press Inc. 2000

Authors and Affiliations

  1. 1.Medical Oncology-Advanced TherapeuticsBritish Columbia Cancer AgencyVancouverCanada

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