Formulation and Delivery of Nucleic Acids

  • H. E. J. Hofland
  • L. Huang
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 137)


The aim of gene therapy is to correct diseases at their origin by delivery and subsequent expression of exogenous DNA, which encodes for a missing or defective gene product. Two distinct strategies for DNA delivery can be employed. The ex vivo strategy uses the cells of a patient, into which the DNA is introduced in vitro. The genetically modified cells are selected, expanded and, finally, transplanted back into the patient (BERNS et al. 1995). This is a relatively efficient method for gene delivery. Most disorders, however, require direct gene transfer, i.e., delivery of the nucleic acids directly into the affected tissues in vivo. One of the major challenges for the direct gene-transfer approach is to develop a vehicle that is able to protect the nucleic acids from degradation, while delivering the genes of interest to specific tissues and target-cell compartments.


Gene Transfer Cationic Lipid Cationic Liposome Direct Gene Transfer Cholesterol Derivative 
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  1. Acsadi G, Dickson G, Love DR, Jani A, Walsh FS, Gurusinghe A, Wolff JA, Davies KE (1991) Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature 352: 815 – 818PubMedCrossRefGoogle Scholar
  2. Alino SF, Bobadilla M, Crespo J, Lejarreta M (1996) Human alphal-antitrypsin gene transfer to in vivo mouse hepatocytes. Hum Gene Ther 7: 531—536Google Scholar
  3. Andree C, Swain WF, Page CP, Macklin MD, Slama J, Hatzis D, Eriksson E (1994) In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair. Proc Natl Acad Sci USA 91: 12188 – 12192PubMedCrossRefGoogle Scholar
  4. Aoki K, Yoshida T, Sugimura T, Terada M (1995) Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity. Cancer Res 55: 3810 – 3816PubMedGoogle Scholar
  5. Ardehali A, Fyfe A, Laks H, Drinkwater DC, Qiao JH, Lusis AJ (1995) Direct gene transfer into donor hearts at the time of harvest. J Thorac Cardiovasc Surg 109: 716 – 720PubMedCrossRefGoogle Scholar
  6. Barthel F, Remy JS, Loeffler JP, Behr JP (1993) Gene transfer optimization with lipospermine-coated DNA. DNA Cell Biol 12: 553 – 560PubMedCrossRefGoogle Scholar
  7. Behr JP, Demeneix B, Loeffler JP, Perez-Mutul J (1989) Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA. Proc Natl Acad Sci USA 86: 6982 – 6986PubMedCrossRefGoogle Scholar
  8. Berns AJM, Clift S, Cohen LK, Donehower RC, Dranoff G, Hauda KM, Jaffee EM, Lazenby AJ, Levitsky HI, Marshall FF, Mulligan RC, Nelson WG, Owens AH, Pardoll DM, Parry G, Partin AH, Piantadosi S, Simons JW, Zabora JR (1995) Clinical Protocol: Phasel study of non-peplicating autologous tumor cell injections using cells prepared with or without GM-CSF gene transduction in patients with metastatic renal cell carcinoma. Hum Gene Ther 6: 347 – 368PubMedCrossRefGoogle Scholar
  9. Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci USA 92: 7297 – 7301PubMedCrossRefGoogle Scholar
  10. Brigham KL, Schreier H (1993) Cationic liposomes and DNA delivery. J Liposome Res 3: 31 – 49CrossRefGoogle Scholar
  11. Buschle M, Cotten M, Kirlappos H, Meehtler K, Schaffner G, Zauner W, Birnstiel ML, Wagner E (1995) Receptor-mediated gene transfer into human T lymphocytes via binding of DNA/CD3 antibody particles to the CD3 T cell receptor complex. Hum Gene Ther 6: 753 – 761PubMedCrossRefGoogle Scholar
  12. Cao L, Zheng ZC, Zhao YC, Jiang ZH, Liu ZG, Chen SD, Zhou CF, Liu XY (1995) Gene therapy of parkinson disease model rat by direct injection of plasmid DNA- lipofectin complex. Hum Gene Ther 6: 1497 – 1501PubMedCrossRefGoogle Scholar
  13. Capecchi MR (1980) High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell 22: 479 – 488PubMedCrossRefGoogle Scholar
  14. Caplen NJ, Alton EWFW, Middleton PG, Dorin JR, Stevenson BJ, Gao X, Durham SR, Jeffery PK, Hodson ME, Coutelle C, Huang L, Porteous DJ, Williamson R, Geddes DM (1995) Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nat Med 1: 39 – 46PubMedCrossRefGoogle Scholar
  15. Curiel DT, Wagner E, Cotten M, Birnstiel ML, Agarwal S, Li C (1992) High-efficiency gene transfer mediated by adenovirus coupled to DNA-polylysine complexes. Hum Gene Ther 3: 147 – 154PubMedCrossRefGoogle Scholar
  16. Farhood H, Bottega R, Epand RM, Huang L (1992) Effect of cationic cholesterol derivatives on gene transfer and protein kinase c activity. Biochim Biophys Acta submittedGoogle Scholar
  17. Farhood H, Serbina N, Huang L (1995) The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer. BBA-Biomembranes 1235: 289 – 295PubMedCrossRefGoogle Scholar
  18. Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Lipofection: a highly efficient, lipid mediated DNA- transfection procedure. Proc Natl Acad Sci USA 84: 7413 – 7417PubMedCrossRefGoogle Scholar
  19. Feigner PL, Ringold GM (1989) Cationic liposome-mediated transfection. Nature 337: 387 – 388CrossRefGoogle Scholar
  20. Felgner JH, Kumar R, Sridhar CN, Wheeler CJ, Tsai YJ, Border R, Ramsey P, Martin M, Feigner PL (1994) Enhanced gene delivery and mechanism studies with novel series of cationic lipid formulations. J Biol Chem 269: 2550 – 2561PubMedGoogle Scholar
  21. Ferkol R, Kaetzel CS, Davis PB (1993) Gene transfer into respiratory epithelial cells by targeting the polymeric immunoglobulin receptor. J Clin Invest 92: 2394 – 2400PubMedCrossRefGoogle Scholar
  22. Ferkol T, Perales JC, Eckman E, Kaetzel CS, Hanson RW, Davis PB (1995) Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor. J Clin Invest 95: 493 – 502PubMedCrossRefGoogle Scholar
  23. Gao X, Huang L (1991) A novel cationic liposome reagent for efficient transfection of mammalian cells. Biochem Biophys Res Commun 179: 280 – 285PubMedCrossRefGoogle Scholar
  24. Gao X, Huang L (1993) Cytoplasmic expression of a reporter gene by co-delivery of T7 RNA polymerase and 17 promoter sequence with cationic liposomes. Nucleic Acids Res 21: 2867 – 2872PubMedCrossRefGoogle Scholar
  25. Gao L, Wagner E, Cotten M, Agarwal S, Harris C, Romer M, Miller L, Hu P, Curiel D (1993) Direct in vivo gene transfer to airway epithelium employing adenovirus- polylysine-DNA complexes. Hum Gene Ther 4: 17 – 24PubMedCrossRefGoogle Scholar
  26. Gao X, Jaffurs D, Robbins PD, Huang L (1994) A sustained, cytoplasmic transgene expression system delivered by cationic liposomes. Biochem Biophys Res Commun 200: 1201 - 1206PubMedCrossRefGoogle Scholar
  27. Gao X, Huang L (1995) Cationic liposome-mediated gene transfer. Gene Ther 2: 710 – 722PubMedGoogle Scholar
  28. Guo LSS, Radhakrishnan R, Redemann CT, Brunette EN, Debs RJ (1993) Cationic liposomes containing noncytotoxic phospholipid and cholesterol derivatives. J Liposome Res 3: 51 – 70CrossRefGoogle Scholar
  29. Haensler J, Szoka FC (1993a) Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. Bioconjugate Chem 4: 372 – 379CrossRefGoogle Scholar
  30. Haensler J, Szoka FC (1993b) Synthesis and characterization of a trigalactosylated bisacridine compound to target DNA to hepatocytes. Bioconjugate Chem 4: 85 – 93CrossRefGoogle Scholar
  31. Hara T, Aramaki Y, Takada S, Koike K, Tsuchiya S (1995a) Receptor-mediated transfer of pSV2CAT DNA to a human hepatoblastoma cell line HepG2 using asialofetuin-labeled cationic liposomes. Gene 159: 167 – 174CrossRefGoogle Scholar
  32. Hara T, Aramaki Y, Takada S, Koike K, Tsuchiya S (1995b) Receptor-mediated transfer of pSV2CAT DNA to mouse liver cells using asialofetuin-labeled liposomes. Gene Ther 2: 784 – 788Google Scholar
  33. Hart SL, Harbottle RP, Cooper R, Miller A, Williamson R, Coutelle C (1995) Gene delivery and expression mediated by an integrin-binding peptide. Gene Ther 2: 552 – 554PubMedGoogle Scholar
  34. Hawley-Nelson P, Ciccarone V, Gebeyehu G, lessee J, Feigner PL (1993) LipofectAMINE reagent: a new, higher efficiency polycationic liposome transfec- tion reagent. Focus 15: 80Google Scholar
  35. Hickman MA, Malone RW, Lehmann-Buinsma K, Sih TR, Knoell D, Szoka FC, Walzern R, Carlson DM, Powell JS (1994) Gene expression following direct injection of DNA into liver. Hum Gene Ther 5: 1477 – 1483PubMedCrossRefGoogle Scholar
  36. Hickman MA, Malone RW, Lehmann-Buinsma K, Sih TR, Knoell D, Szoka FC, Walzern R, Carlson DM, Powell JS (1994) Gene expression following direct injection of DNA into liver. Hum Gene Ther 5: 1477 – 1483PubMedCrossRefGoogle Scholar
  37. Hyde S, Gill D, Higgins C, Trezise A, MacVinish LJ, Cuthbert AW, Ratcliff R, Evans MJ, Colledge WH (1993) Correction of the ion transport defect in cystic fibrosis transgenic mice by gene therapy. Nature 362: 250 – 255PubMedCrossRefGoogle Scholar
  38. Ito A, Miyazoe R, Mitoma J, Akao T, Osaki T, Kunitake T (1990) Synthetic cationic amphiphiles for liposome-mediated DNA transfection. Biochem Int 22: 235 – 241PubMedGoogle Scholar
  39. Jiao S, Williams P, Berg RK, Hodgeman BA, Liu L, Repetto G, Wolff JA (1992) Direct gene transfer into nonhuman primate myofibers in vivo. Hum Gene Ther 3: 21 – 33PubMedCrossRefGoogle Scholar
  40. Kaneda Y, Uchida T, Kim J, Ishiura M, Okada Y (1987) The improved efficient method for introducing macromolecules into cells using HVJ (Sendai virus) liposomes with gangliosides. Exp Cell Res 173: 56 – 69PubMedCrossRefGoogle Scholar
  41. Kaneda Y, Iwai K, Uchida T (1989) Introduction and expression of the human insulin gene in adult rat liver. J Biol Chem 264: 12126 – 12129PubMedGoogle Scholar
  42. Kato K, Dohi Y, Yoneda Y, Yamamura K, Okada Y, Nakanishi M (1993) Use of the hemagglutinating virus of Japan (HVJ)-liposome method for analysis of infiltrating lymphocytes induced by hepatitis B virus gene expression in liver tissue. Biochim Biophys Acta 1182: 283 – 290PubMedGoogle Scholar
  43. Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA, Baker JR (1996) Efficient transfer of genetic material into mammalian cells using starburst polyamidoamine dendrimers. Proc Natl Acad Sci USA 93: 4897 – 4902PubMedCrossRefGoogle Scholar
  44. Kupfer JM, Ruan XM, Liu G, Matloff J, Forrester J, Chaux A (1994) High-efficiency gene transfer to autologous rabbit jugular vein grafts using adenovirus-transferrin/ polylysine-DNA complexes. Hum Gene Ther 5: 1437 – 1443PubMedCrossRefGoogle Scholar
  45. Lee RJ, Huang L (1996) Folate-targeted, anionic liposome-entrapped polylysine- condensed DNA for tumor cell-specific gene transfer. J Biol Chem 271: 8481 – 8487PubMedCrossRefGoogle Scholar
  46. Legendre J-Y, Szoka FC (1992) Delivery of plasmid DNA into mammalian cell lines using pH-sensitive liposomes: comparison with cationic liposomes. Pharm Res 9: 1235 – 1242PubMedCrossRefGoogle Scholar
  47. Legendre J-Y, Szoka F (1993) Cyclic amphipathic peptide-DNA complexes mediate high-efficiency transfection of adherent mammalian cells. Proc 90: 893 – 897Google Scholar
  48. Leibiger B, Leibiger I, Sarrach D, Zuhlke H (1991) Expression of exogenous DNA in rat liver cells after liposome-mediated transfection in vivo. Biochem Biophys Res Commun 174: 1223 – 1231PubMedCrossRefGoogle Scholar
  49. Li AP, Myers CA, Kaminski DL (1992) Gene transfer in primary cultures of human hepatocytes in vitro. Cell 28A: 373 - 375Google Scholar
  50. Liang WW, Shi X, Deshpande D, Malanga CJ, Rojanasakul Y (1996) Oligonucleotide targeting to alveolar macrophages by mannose receptor-mediated endocytosis. Biochim Biophys Acta 1279: 227 – 234PubMedCrossRefGoogle Scholar
  51. Litzinger DC, Huang L (1992) Phosphatidylethanolamine liposomes: drug delivery, gene transfer and immunodiagnostic applications. Biochim Biophys Acta 1113: 201 – 227PubMedGoogle Scholar
  52. Liu Y, Liggitt D, Zhong W, Tu G, Gaensler K, Debs R (1995) Cationic liposome mediated intravenous gene delivery. J Biochem 270: 24864 – 24870Google Scholar
  53. Lu D, Benjamin R, Kim M, Conry RM, Curiel DT (1994) Optimization of methods to achieve mRNA-mediated transfection of tumor cells in vitro and in vivo employing cationic liposome vectors. Cancer Gene Ther 1: 245 – 252PubMedGoogle Scholar
  54. Mahato RI, Kawabata K, Takakura Y, Hashida M (1995a) Control of in vivo disposition of plasmid DNA using cationic liposomes. J Drug Target 3: 149 – 157CrossRefGoogle Scholar
  55. Mahato RI, Kawabata K, Nomura T, Takakura Y, Hashida M (1995b) Physicochemical and pharmacokinetic characteristics of plasmid DNA/cationic liposome complexes. J Pharm Sci 84: 1267 – 1271CrossRefGoogle Scholar
  56. Midoux P, Mendes C, Legrand A, Raimond J, Mayer R, Monsigny M, Roche AC (1993) Specific gene transfer mediated by lactosylated poly-L-lysine into hepatoma cells. Nucleic Acids Res 21: 871 – 878PubMedCrossRefGoogle Scholar
  57. Missol E, Sochanik A, Szala S (1995) Introduction of murine 11-4 gene into B16(F10) melanoma tumors by direct gene transfer with DNA-liposome complexes. Cancer Lett 97: 189 – 193PubMedCrossRefGoogle Scholar
  58. Moradpour D, Schauer JI, Zurawski VR, Wands JR, Boutin RH (1996) Efficient gene transfer into mammalian cells with cholesteryl-spermidine. Biochem Biophys Res Commun 221: 82 – 88PubMedCrossRefGoogle Scholar
  59. Morishita R, Gibbons GH, Kaneda Y^Ogihara T, Dzau VJ (1993) Novel in vitro gene transfer method for study of local modulators in vascular smooth muscle cells. Hypertension 21: 894 – 899Google Scholar
  60. Mulligan R (1993) The basic science of gene therapy. Science 260: 926 – 932PubMedCrossRefGoogle Scholar
  61. Muzyczka N (1992) The use of adeno-associated virus as a general transduction vector for mammalian cells. Curr Top Microbiol Immunol 158: 97 – 129PubMedGoogle Scholar
  62. Nabel G, Chang A, Nabel EG, Plautz G, Fox BA, Huang L, Shu S (1992) Immunotherapy of malignancy by in vivo gene transfer into tumors. Hum Gene Ther 3: 399 – 410CrossRefGoogle Scholar
  63. Nabel G, Nabel E, Yang Z, Fox B, Plautz G, Gao X, Huang L, Shu S, Gordon D, Chang A (1993) Direct gene transfer with DNA-Liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc 90: 11307 – 11311Google Scholar
  64. Nicolau C, Le Pape A, Soriano P, Fargette F, Juhel MF (1983) In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I. Proc Natl Acad Sci USA 80: 1068 – 1072PubMedCrossRefGoogle Scholar
  65. Ostro M, Giacomoni D, Dray S (1977) Incorporation of high molecular weight RNA into large artificial lipid vesicles. Biochem Biophys Res Commun 76: 836 – 842PubMedCrossRefGoogle Scholar
  66. Perales JC, Ferkol T, Beegen H, Ratnoff OD, Hanson RW (1994) Gene transfer in vivo: Sustained expression and regultaion of genes introduced into the liver by receptor-targeted uptake. Proc Natl Acad Sci USA 91: 4086 – 4090PubMedCrossRefGoogle Scholar
  67. Plautz G, Nabel E, Nabel G (1993) Liposome Mediated Gene Transfer Into Vascular Cells. J Liposome Res 3: 179 – 199CrossRefGoogle Scholar
  68. Rajawalia R, Webber J, Naftilan J, Chapman GD, Naftilan AJ (1995) Enhancement of liposome-mediated gene transfer into vascular tissue by replication deficient adenovirus. Gene Ther 2: 521 – 530Google Scholar
  69. Remy J-S, Sirlin C, Vierling P, Behr JP (1994) Gene transfer with a series of lipophilic DNA-binding molecules. Bioconjugate Chem 5: 647 – 654CrossRefGoogle Scholar
  70. Remy JS, Kichler A, Mordvinov V, Schuber F, Behr JP (1995) Targeted gene transfer into hepatoma cells with lipopolyamine-condensed DNA particles presenting galactose ligands: a stage toward artificial viruses. Proc Natl Acad Sci USA 92: 1744 – 1748PubMedCrossRefGoogle Scholar
  71. Ross GF, Morris RE, Ciraolo G, Huelsman K, Bruno M, Whitsett JA, Baatz JE, Korfhagen TR (1995) Surfactant protein A-polylysine conjugates for delivery of DNA to airway cells in culture. Hum Gene Ther 6: 31 – 40PubMedCrossRefGoogle Scholar
  72. Sawa Y, Suzuki K, Bai HZ, Shirakura R, Morishita R, Kaneda Y, Matsuda H (1995) Efficiency of in vivo gene transfection into transplanted rat heart by coronary infusion of HVJ liposome. Circulation 92: 479 – 482Google Scholar
  73. Schwartz B, Benoist C, Abdallah B, Scherman D, Behr JP, Demeneix B (1995) Lipospermine-based gene transfer into the newborn mouse brain is optimized by a low lipospermine/DNA charge ratio. Hum Gene Ther 6: 1515 – 1524PubMedCrossRefGoogle Scholar
  74. Shockett PE, Schatz DG (1996) Diverse strategies for tetracycline-regulated inducible gene expression. Proc Natl Acad Sci USA 93: 5173 – 5176PubMedCrossRefGoogle Scholar
  75. Son K, Huang L (1994) Exposure ofhuman ovarian carcinoma to cisplatin transiently sensitizes the tumor cells for liposome-mediated gene transfer. Proc Natl Acad Sci USA 91: 12669 – 12672PubMedCrossRefGoogle Scholar
  76. Soriano P, Legrand A, Spanjer H, Londos-Gagliardi D, Roerdink F, Scherphof G, Nicolau C (1983) Targeted and non-targeted liposomes for in vivo transfer to rat liver cells of a plasmid containing preproinsulin I gene. Proc Natl Acad Sci USA 80: 11277 – 11281Google Scholar
  77. Stankovics J, Crane AM, Andrews E, Wu CH, Wu GY, Ledley FD (1994) Overexpression of human methylmalonyl CoA mutase in mice after in vivo gene transfer with asialoglycoprotein/polylysine/DNA complexes. Hum Gene Ther 5: 1095 – 1104PubMedCrossRefGoogle Scholar
  78. Sternberg B, Sorgi FL, Huang L (1994) New structures in complex formation between DNA and cationic liposomes visualized by freeze-fracture electron microscopy. FEBS Lett 356: 361 – 366PubMedCrossRefGoogle Scholar
  79. Stribling R, Brunette E, Liggitt D, Gaensler K, Debs R (1992) Aerosol gene delivery in vivo. Proc 89: 11277 – 11281Google Scholar
  80. Sun WH, Burkholder JK, Sun J, Culp J, Lu XG, Pugh TD, Ershler WB, Yang NS (1995) In vivo cytokine gene transfer by gene gun reduces tumor growth in mice. Proc Natl Acad Sci USA 92: 2889 – 2893PubMedCrossRefGoogle Scholar
  81. Takehara T, Hayashi N, Miyamoto Y, Yamamoto M, Mita E, Fusamoto H, Kamada T (1995) Expression of the hepatitis C virus genome in rat liver after cationic liposome-mediated In vivo gene transfer. Hepatology 21: 746 – 751PubMedGoogle Scholar
  82. Thierry AR, Lunardi-Isakandar Y, Bryant JL, Rabinovich P, Gallo RC, Mahan LC (1995) Systemic gene therapy: biodistribution and long-term expression of a transgene in mice. Proc Natl Acad Sci USA 92: 9742 – 9746PubMedCrossRefGoogle Scholar
  83. Tomita N, Higaki J, Morishita R, Kato K, Mikami H, Kaneda Y, Ogihara T (1992) Direct in vivo gene introduction into rat kidney. Biochem Biophys Res Commun 186: 129 – 134PubMedCrossRefGoogle Scholar
  84. Tomita N, Higaki J, Kaneda Y, Yu H, Morishita R, Mikami H, Ogihara T (1993) Hypertensive rats produced by in vivo introduction of the human renin gene. Circ Res 73: 898 – 905PubMedGoogle Scholar
  85. Trubetskoy VS, Torchilin VP, Kennel S, Huang L (1992a) Cationic liposomes enhance targeted delivery and expression of exogenous DNA mediated by N-terminal modified poly(L-lysine)-antibody conjugate in mouse lung endothelial cells. Biochim Biophys Acta 1131: 311 – 313Google Scholar
  86. Trubetskoy VS, Torchilin VP, Kennel SJ, Huang L (1992b) Use of N-terminal modified poly(L-lysine)-antibody conjugate as a carrier for targeted gene delivery in mouse lung endothelial cells. Bioconjugate Cliem 3: 323 – 327CrossRefGoogle Scholar
  87. Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, De Witt CM, Friedman A (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259: 1745 – 1749PubMedCrossRefGoogle Scholar
  88. Wagner E, Cotten M, Mechtler K, Kirlappos H, Birnstiel ML (1991a) DNA binding transferrin conjugates as funtional gene-delivery agents: synthesis by linkage of polylysine or ethidium homodimer to the transferrin carbohydrate moiety. Bioconjugate Chem 2: 226 – 231CrossRefGoogle Scholar
  89. Wagner E, Cotten M, Foisner R, Birnstiel ML (1991b) Transferrin-polycation-DNA complexes: The effect of poly-cations on the structure of the complex and DNA delivery to cells. Proc Natl Acad Sci USA 88: 4255 – 4259CrossRefGoogle Scholar
  90. Wagner E, Zatloukal K, Cotten M, Kirlappos H, Mechtler K, Curiel DT, Birnstiel ML (1992) Coupling of adenovirus to transferrin-polylysine-DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. Proc Natl Acad Sci USA 89: 6099 – 6103PubMedCrossRefGoogle Scholar
  91. Wang C-Y, Huang L (1987a) Plasmid DNA adsorbed to pH-sensitive liposomes efficiently transforms the target cells. Biochem Biophys Res Commun 147: 980 – 985CrossRefGoogle Scholar
  92. Wang C-Y, Huang L (1987b) pH-sensitive immunoliposomes mediate target-cell- specific delivery and controlled expression of a foreign gene in mouse. Proc Natl Acad Sci USA 84:7851–7855Google Scholar
  93. Wang C-Y, Huang L (1989) Highly efficient DNA delivery mediated by pH-sensitive immunoliposomes. Biochemistry 28: 9508 – 9514PubMedCrossRefGoogle Scholar
  94. Wells D (1993) Improved gene transfer by direct plasmid injection associated with regeneration in mouse skeletal muscle. FEBS Lett 332: 179 – 182PubMedCrossRefGoogle Scholar
  95. Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Feigner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247: 1465 – 1468PubMedCrossRefGoogle Scholar
  96. Wolff JA, Williams P, Acsadi G, Jiao S, Jani A, Chong W (1991) Conditions affecting direct gene transfer into rodent muscle in vivo. BioTechniques 11: 474 – 485PubMedGoogle Scholar
  97. Wynshaw-Boris A, Lugo TG, Short JM, Fournier RE, Hanson RW (1984) Identification of a cAMP regulatory region in the gene for rat cytosolic phosphoenolpyru- vate carboxykinase (GTP). Use of chimeric genes transfected into hepatoma cells. J Biol Chem 259: 12161 – 12169PubMedGoogle Scholar
  98. Xu Y, Szoka FC (1996) Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 35: 5616 – 5623PubMedCrossRefGoogle Scholar
  99. Yang N-S, Burkholder J, Roberts B, Martineil B, McCabe D (1990) In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad Sci USA 87: 9568 – 9572PubMedCrossRefGoogle Scholar
  100. Yoshimura K, Rosenfeld MA, Nakamura H, Scherer EM, Pavirani A, Lecocq JP, Crystal RG (1992) Expression of the human cystic fibrosis transmembrane conductance regulator gene in the mouse lung after in vivo intratracheal plasmid- mediated gene transfer. Nucleic Acids Res 20: 3233 – 3240PubMedCrossRefGoogle Scholar
  101. Yu DH, Matin A, Xia WY, Sorgi F, Huang L, Hung MC (1995) Liposome-mediated in vivo El A gene transfer suppressed dissemination of ovarian cancer cells that overexpress HER-2/neu. Oncogene 11: 1383 – 1388PubMedGoogle Scholar
  102. Zabner J, Fasbender AJ, Moninger T, Poellinger KA, Welsh MJ (1995) Cellular and molecular barriers to gene transfer by a cationic lipid. J Biol Chem 270: 18997 – 19007PubMedCrossRefGoogle Scholar
  103. Zhou X, Klibanov A, Huang L (1991) Lipophilic polylysines mediate efficient DNA transfection in ammalian cells. Biochim Biophys Acta 1065: 8 – 14PubMedCrossRefGoogle Scholar
  104. Zhou X, Huang L (1992a) Liposomes containing lipopolylysine as a vehicle for gene transfer II: mechanism of action. J Biol Chem submittedGoogle Scholar
  105. Zhou X, Huang L (1992b) Targeted delivery of DNA by liposomes and polymers. J Control Rel 19: 269 – 274CrossRefGoogle Scholar
  106. Zhou X, Klibanov A, Huang L (1992c) Improved encapsulation of DNA in pH-sensitive liposomes for transfection. J Liposome Res 2: 125 – 139CrossRefGoogle Scholar
  107. Zhou X, Huang L (1994) DNA transfection mediated by cationic liposomes containing lipopolylysine: characterization and mechanism of action. Biochim Biophys Acta 1189: 195 – 203PubMedCrossRefGoogle Scholar
  108. Zhu N, Liggit D, Liu Y, Debs R (1993) Systemic gene expression after intravenous DNA delivery into adult mice. Science 261: 209 – 211PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • H. E. J. Hofland
  • L. Huang

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