The AAPS Journal

, Volume 9, Issue 1, pp E92–E104 | Cite as

Nonviral gene delivery: What we know and what is next

Article

Abstract

Gene delivery using nonviral approaches has been extensively studied as a basic tool for intracellular gene transfer and gene therapy. In the past, the primary focus has been on application of physical, chemical, and biological principles to development of a safe and efficient method that delivers a transgene into target cells for appropriate expression. This review summarizes the current status of the most commonly used nonviral methods, with an emphasis on their mechanism of action for gene delivery, and their advantages and limitations for gene therapy applications. The technical aspects of each delivery system are also reviewed, with a focus on how to achieve optimal delivery efficiency. A brief discussion of future development and further improvement of the current systems is intended to stimulate new ideas and encourage rapid advancement in this new and promising field.

Keywords

Gene delivery gene therapy nonviral vectors transfection 

References

  1. 1.
    Wolff JA, Malone RW, Williams P, et al. Direct gene transfer into mouse musclein vivo.Science. 1990;247:1465–1468.PubMedGoogle Scholar
  2. 2.
    Heller LC, Ugen K, Heller R. Electroporation for targeted gene transfer.Expert Opin Drug Deliv. 2005;2:255–268.PubMedGoogle Scholar
  3. 3.
    Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH. Gene transfer into mouse lyoma cells by electroporation in high electric fields.EMBO J. 1982;1:841–845.PubMedGoogle Scholar
  4. 4.
    Yang NS, Burkholder J, Roberts B, Martinell B, McCabe D.In vivo andin vitro gene transfer to mammalian somatic cells by particle bom bardment.Proc Natl Acad Sci USA. 1990;87:9568–9572.PubMedGoogle Scholar
  5. 5.
    Yang NS, Sun WH. Gene gun and other non-viral approaches for cancer gene therapy.Nat Med. 1995;1:481–483.PubMedGoogle Scholar
  6. 6.
    Lawrie A, Brisken AF, Francis SE, Cumberland DC, Crossman DC, Newman CM. Microbubble-enhanced ultrasound for vascular gene delivery.Gene Ther. 2000;7:2023–2027.PubMedGoogle Scholar
  7. 7.
    Lin F, Song Y, Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA.Gene Ther. 1999;6:1258–1266.Google Scholar
  8. 8.
    Zhang G, Budker V, Wolff JA. High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA.Hum Gene Ther. 1999;10:1735–1737.PubMedGoogle Scholar
  9. 9.
    Neu M, Fischer D, Kissel T. Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives.J Gene Med. 2005;7:992–1009.PubMedGoogle Scholar
  10. 10.
    Liu D, Ren T, Gao X. Cationic transfection lipids.Curr Med Chem. 2003;10:1307–1315.PubMedGoogle Scholar
  11. 11.
    Huang L, Hung MC, Wagner E.Nonviral Vectors for Gene Therapy. San Diego, CA: Academic Press; 1999.Google Scholar
  12. 12.
    Mahato RI, Kim SW.Pharmaceutical Perspectives of Nucleic Acid-Based Therapeutics. London, UK: Taylor & Francis; 2002.Google Scholar
  13. 13.
    Hickman MA, Malone RW, Lehmann-Bruinsma K, et al. Gene expression following direct injection of DNA into liver.Hum Gene Ther. 1994;5:1477–1483.PubMedGoogle Scholar
  14. 14.
    Zhang G, Vargo D, Budker V, Armstrong N, Knechtle S, Wolff JA. Expression of naked plasmid DNA injected into the afferent and efferent vessels of rodent and dog livers.Hum Gene Ther. 1997;8:1763–1772.PubMedGoogle Scholar
  15. 15.
    Budker V, Zhang G, Knechtle S, Wolff JA. Naked DNA delivered intraportally expresses efficiently in hepatocytes.Gene Ther. 1996;3:593–598.PubMedGoogle Scholar
  16. 16.
    Choate KA, Khavari PA. Direct cutaneous gene delivery in a human genetic skin disease.Hum Gene Ther. 1997;8:1659–1665.PubMedGoogle Scholar
  17. 17.
    Meyer KB, Jr, Thompson MM, Jr, Levy MY, Jr, Barron LG, Jr, Szoka FC, Jr. Intratracheal gene delivery to the mouse airway: characterization of plasmid DNA expression and pharmacokinetics.Gene Ther. 1995;2:450–460.PubMedGoogle Scholar
  18. 18.
    Sato Y, Yamauchi N, Takahashi M, et al. In vivo gene delivery to tumor cells by transferrin-streptavidin-DNA conjugate.FASEB J. 2000;14:2108–2118.PubMedGoogle Scholar
  19. 19.
    Schughart K, Rasmussen UB. Solvoplex synthetic vector for intrapulmonary gene delivery. Preparation and use.Methods Mol Med. 2002;69:83–94.PubMedGoogle Scholar
  20. 20.
    Schughart K, Bischoff R, Rasmussen UB, et al. Solvoplex: a new type of synthetic vector for intrapulmonary gene delivery.Hum Gene Ther. 1999;10:2891–2905.PubMedGoogle Scholar
  21. 21.
    Desigaux L, Gourden C, Bello-Roufai M, et al. Nonionic amphiphilic block copolymers promote gene transfer to the lung.Hum Gene Ther. 2005;16:821–829.PubMedGoogle Scholar
  22. 22.
    Freeman DJ, Niven RW. The influence of sodium glycocholate and other additives on the in vivo transfection of plasmid DNA in the lungs.Pharm Res. 1996;13:202–209.PubMedGoogle Scholar
  23. 23.
    Lemoine JL, Farley R, Huang L. Mechanism of efficient transfection of the nasal airway epithelium by hypotonic shock.Gene Ther. 2005;12:1275–1282.PubMedGoogle Scholar
  24. 24.
    Ross GF, Bruno MD, Uyeda M, et al. Enhanced reporter gene expression in cells transfected in the presence of DMI-2, an acid nuclease inhibitor.Gene Ther. 1998;5:1244–1250.PubMedGoogle Scholar
  25. 25.
    Walther W, Stein U, Siegel R, Fichtner I, Schlag PM. Use of the nuclease inhibitor aurintricarboxylic acid (ATA) for improved non-viral intratumoral in vivo gene transfer by jet-injection.J Gene Med. 2005;7:477–485.PubMedGoogle Scholar
  26. 26.
    Glasspool-Malone J, Malone RW. Marked enhancement of direct respiratory tissue transfection by aurintricarboxylic acid.Hum Gene Ther. 1999;10:1703–1713.PubMedGoogle Scholar
  27. 27.
    O'Brien J, Lummis SC. An improved method of preparing microcarriers for biolistic transfection.Brain Res Brain Res Protoc. 2002;10:12–15.PubMedGoogle Scholar
  28. 28.
    Hasson E, Slovatizky Y, Shimoni Y, Falk H, Panet A, Mitrani E. Solid tissues can be manipulated ex vivo and used as vehicles for gene therapy.J Gene Med. 2005;7:926–935.PubMedGoogle Scholar
  29. 29.
    Dean DA, Machado-Aranda D, Blair-Parks K, Yeldandi AV, Young JL. Electroporation as a method for high-level nonviral gene transfer to the lung.Gene Ther. 2003;10:1608–1615.PubMedGoogle Scholar
  30. 30.
    Magin-Lachmann C, Kotzamanis G, D'Aiuto L, Cooke H, Huxley C, Wagner E. In vitro and in vivo delivery of intact BAC DNA— comparison of different methods.J Gene Med. 2004;6:195–209.PubMedGoogle Scholar
  31. 31.
    Molnar MJ, Gilbert R, Lu Y, et al. Factors influencing the efficacy, longevity, and safety of electroporation-assisted plasmid-based gene transfer into mouse muscles.Mol Ther. 2004;10:447–455.PubMedGoogle Scholar
  32. 32.
    McMahon JM, Wells DJ. Electroporation for gene transfer to skeletal muscles: current status.Bio Drugs. 2004;18:155–165.Google Scholar
  33. 33.
    McMahon JM, Signori E, Wells KE, Fazio VM, Wells DJ. Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase—increased expression with reduced muscle damage.Gene Ther. 2001;8:1264–1270.PubMedGoogle Scholar
  34. 34.
    Sakai M, Nishikawa M, Thanaketpaisarn O, Yamashita F, Hashida M. Hepatocyte-targeted gene transfer by combination of vascularly delivered plasmid DNA andin vivo electroporation.Gene Ther. 2005;12:607–616.PubMedGoogle Scholar
  35. 35.
    Durieux AC, Bonnefoy R, Busso T, Freyssenet D.In vivo gene electrotransfer into skeletal muscle: effects of plasmid DNA on the occurrence and extent of muscle damage.J Gene Med. 2004;6:809–816.PubMedGoogle Scholar
  36. 36.
    Gissel H, Clausen T. Excitation-induced Ca2+ influx and skeletal muscle cell damage.Acta Physiol Scand. 2001;171:327–334.PubMedGoogle Scholar
  37. 37.
    Kim HJ, Greenleaf JF, Kinnick RR, Bronk JT, Bolander ME. Ultrasound-mediated transfection of mammalian cells.Hum Gene Ther. 1996;7:1339–1346.PubMedGoogle Scholar
  38. 38.
    Liang HD, Lu QL, Xue SA, et al. Optimisation of ultrasound-mediated gene transfer (sonoporation) in skeletal muscle cells.Ultrasound Med Biol. 2004;30:1523–1529.PubMedGoogle Scholar
  39. 39.
    Huber PE, Jenne J, Debus J, Wannenmacher MF, Pfisterer P. A comparison of shock wave and sinusoidal-focused ultrasound-induced localized transfection of HeLa cells.Ultrasound Med Biol. 1999;25:1451–1457.PubMedGoogle Scholar
  40. 40.
    Nozaki T, Jr, Ogawa R, Jr, Feril LB, Jr, Kagiya G, Fuse H, Kondo T. Enhancement of ultrasound-mediated gene transfection by membrane modification.J Gene Med. 2003;5:1046–1055.PubMedGoogle Scholar
  41. 41.
    Ogawa R, Jr, Kagiya G, Jr, Feril LB, Jr, et al. Ultrasound mediated intravesical transfection enhanced by treatment with lidocaine or heat.J Urol. 2004;172:1469–1473.PubMedGoogle Scholar
  42. 42.
    Koch S, Pohl P, Cobet U, Rainov NG. Ultrasound enhancement of liposome-mediated cell transfection is caused by cavitation effects.Ultrasound Med Biol. 2000;26:897–903.PubMedGoogle Scholar
  43. 43.
    Anwer K, Kao G, Proctor B, et al. Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration.Gene Ther. 2000;7:1833–1839.PubMedGoogle Scholar
  44. 44.
    Unger EC, Hersh E, Vannan M, Matsunaga TO, McCreery T. Local drug and gene delivery through microbubbles.Prog Cardiovasc Dis. 2001;44:45–54.PubMedGoogle Scholar
  45. 45.
    Zhang G, Gao X, Song YK, et al. Hydroporation as the mechanism of hydrodynamic delivery.Gene Ther. 2004;11:675–682.PubMedGoogle Scholar
  46. 46.
    Al-Dosari MS, Knapp JE, Liu D. Hydrodynamic delivery.Adv Genet. 2005;54:65–82.PubMedGoogle Scholar
  47. 47.
    Miao CH, Thompson AR, Loeb K, Ye X. Long-term and therapeutic-level hepatic gene expression of human factor IX after naked plasmid transferin vivo.Mol Ther. 2001;3:947–957.PubMedGoogle Scholar
  48. 48.
    Miao CH, Ye X, Thompson AR. High-level factor VIII gene expressionin vivo achieved by nonviral liver-specific gene therapy vectors.Hum Gene Ther. 2003;14:1297–1305.PubMedGoogle Scholar
  49. 49.
    Zhang G, Song YK, Liu D. Long-term expression of human alpha1-antitrypsin gene in mouse liver achieved by intravenous administration of plasmid DNA using a hydrodynamics-based procedure.Gene Ther. 2000;7:1344–1349.PubMedGoogle Scholar
  50. 50.
    Alino SF, Crespo A, Dasi F. Long-term therapeutic levels of human alpha-1 antitrypsin in plasma after hydrodynamic injection of nonviral DNA.Gene Ther. 2003;10:1672–1679.PubMedGoogle Scholar
  51. 51.
    Stoll SM, Sclimenti CR, Baba EJ, Meuse L, Kay MA, Calos MP. Epstein-Barr virus/human vector provides high-level, long-term expression of alpha1-antitrypsin in mice.Mol Ther. 2001;4:122–129.PubMedGoogle Scholar
  52. 52.
    Jiang J, Yamato E, Miyazaki J. Intravenous delivery of naked plasmid DNA forin vivo cytokine expression.Biochem Biophys Res Commun. 2001;289:1088–1092.PubMedGoogle Scholar
  53. 53.
    Yang J, Chen S, Huang L, Michalopoulos GK, Liu Y. Sustained expression of naked plasmid DNA encoding hepatocyte growth factor in mice promotes liver and overall body growth.Hepatology. 2001;33:848–859.PubMedGoogle Scholar
  54. 54.
    Maruyama H, Higuchi N, Kameda S, Miyazaki J, Gejyo F. Rat liver-targeted naked plasmid DNA transfer by tail vein injection.Mol Biotechnol. 2004;26:165–172.PubMedGoogle Scholar
  55. 55.
    Eastman SJ, Baskin KM, Hodges BL, et al. Development of catheter-based procedures for transducing the isolated rabbit liver with plasmid DNA.Hum Gene Ther. 2002;13:2065–2077.PubMedGoogle Scholar
  56. 56.
    Alino SF, Herrero MJ, Noguera I, Dasi F, Sanchez M. Pig liver gene therapy by noninvasive interventionist catheterism.Gene Ther. 2007;14:334–343.PubMedGoogle Scholar
  57. 57.
    Yoshino H, Hashizume K, Kobayashi E. Naked plasmid DNA transfer to the porcine liver using rapid injection with large volume.Gene Ther. 2006;13:1696–1702.PubMedGoogle Scholar
  58. 58.
    Felgner PL, Gadek TR, Holm M, et al. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.Proc Natl Acad Sci USA. 1987;84:7413–7417.PubMedGoogle Scholar
  59. 59.
    Xu Y, Jr, Szoka FC, Jr. Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection.Biochemistry. 1996;35:5616–5623.PubMedGoogle Scholar
  60. 60.
    Farhood H, Serbina N, Huang L. The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer.Biochim Biophys Acta. 1995;1235:289–295.PubMedGoogle Scholar
  61. 61.
    Wrobel I, Collins D. Fusion of cationic liposomes with mammalian cells occurs after endocytosis.Biochim Biophys Acta. 1995;1235:296–304.PubMedGoogle Scholar
  62. 62.
    Litzinger DC, Huang L. Phosphatidylethanolamine liposomes: drug delivery, gene transfer and immunodiagnostic applications.Biochim Biophys Acta. 1992;1113:201–227.PubMedGoogle Scholar
  63. 63.
    El Ouahabi A, Thiry M, Pector V, Fuks R, Ruysschaert JM, Vandenbranden M. The role of endosome destabilizing activity in the gene transfer process mediated by cationic lipids.FEBS Lett. 1997;414:187–192.PubMedGoogle Scholar
  64. 64.
    Behr JP, Demeneix B, Loeffler JP, Perez-Mutul J. Efficient gene transfer into mammalian primary endocrine cells with lipopolyaminecoated DNA.Proc Natl Acad Sci USA. 1989;86:6982–6986.PubMedGoogle Scholar
  65. 65.
    Pedroso de Lima MC, Simoes S, Pires P, Faneca H, Duzgunes N. Cationic lipid-DNA complexes in gene delivery: from biophysics to biological applications.Adv Drug Deliv Rev. 2001:47:277–294.PubMedGoogle Scholar
  66. 66.
    Sternberg B, Sorgi FL, Huang L. New structures in complex formation between DNA and cationic liposomes visualized by freezefracture electron microscopy.FEBS Lett. 1994;356:361–366PubMedGoogle Scholar
  67. 67.
    Lin AJ, Slack NL, Ahmad A, George CX, Samuel CE, Safinya CR. Three-dimensional imaging of lipid gene-carriers: membrane charge density controls universal transfection behavior in lamellar cationic liposome-DNA complexes.Biophys J. 2003;84:3307–3316.PubMedGoogle Scholar
  68. 68.
    Thierry AR, Rabinovich P, Peng B, Mahan LC, Bryant JL, Gallo RC. Characterization of liposome-mediated gene delivery: expression, stability and pharmacokinetics of plasmid DNA.Gene Ther. 1997;4:226–237.PubMedGoogle Scholar
  69. 69.
    Koltover I, Salditt T, Radler JO, Safinya CR. An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery.Science. 1998;281:78–81.PubMedGoogle Scholar
  70. 70.
    Hofland HE, Shephard L, Sullivan SM. Formation of stable cationic lipid/DNA complexes for gene transfer.Proc. Natl Acad Sci USA. 1996;93:7305–7309.PubMedGoogle Scholar
  71. 71.
    Dauty E, Remy JS, Zuber G, Behr JP. Intracellular delivery of nanometric DNA particles via the folate receptor.Bioconjung Chem. 2002;13:831–839.Google Scholar
  72. 72.
    Li S, Tseng WC, Stolz DB, Wu SP, Watkins SC, Huang L. Dynamic changes in the characteristics of cationic lipidic vectors after exposure to mouse serum: implications for intravenous lipofection.Gene Ther. 1999;6:585–594.PubMedGoogle Scholar
  73. 73.
    Simberg D, Weisman S, Talmon Y, Faerman A, Shoshani T, Barenholz Y. The role of organ vascularization and lipoplex-serum initial contact in intravenous murine lipofection.J Biol Chem. 2003;278:39858–39865.PubMedGoogle Scholar
  74. 74.
    Song YK, Liu F, Chu S, Liu D. Characterization of cationic liposome-mediated gene transfer in vivo by intravenous administration.Hum Gene Ther. 1997;8:1585–1594.PubMedGoogle Scholar
  75. 75.
    Templeton NS, Lasic DD, Frederik PM, Strey HH, Roberts DD, Pavlakis GN. Improved DNA: liposome complexes for increased systemic delivery and gene expression.Nat Biotechnol. 1997;15:647–652.PubMedGoogle Scholar
  76. 76.
    Thierry AR, Lunardi-Iskandar Y, Bryant JL, Rabinovich P, Gallo RC, Mahan LC. Systemic gene therapy: biodistribution and long-term expression of a transgene in mice.Proc Natl Acad Sci USA. 1995;92:9742–9746.PubMedGoogle Scholar
  77. 77.
    Hyde SC, Southern KW, Gileadi U, et al. Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis.Gene Ther. 2000;7:1156–1165.PubMedGoogle Scholar
  78. 78.
    Noone PG, Hohneker KW, Zhou Z, et al. Safety and biological efficacy of a lipid-CFTR complex for gene transfer in the nasal epithelium of adult patients with cystic fibrosis.Mol Ther. 2000;1:105–114.PubMedGoogle Scholar
  79. 79.
    Bragonzi A, Dina G, Villa A, et al. Biodistribution and transgene expression with nonviral cationic vector/DNA complexes in the lungs.Gene Ther. 2000;7:1753–1760.PubMedGoogle Scholar
  80. 80.
    Middleton PG, Caplen NJ, Gao X, et al. Nasal application of the cationic liposome DC-Chol: DOPE does not alter ion transport, lung function or bacterial growth.Eur Respir J. 1994;7:442–445.PubMedGoogle Scholar
  81. 81.
    Lee ER, Marshall J, Siegel CS, et al. Detailed analysis of structures and formulations of cationic lipids for efficient gene transfer to the lung.Hum Gene Ther. 1996;7:1701–1717.PubMedGoogle Scholar
  82. 82.
    Duncan JE, Whitsett JA, Horowitz AD. Pulmonary surfactant inhibits cationic liposome-mediated gene delivery to respiratory epithelial cellsin vitro.Hum Gene Ther. 1997;8:431–438.PubMedGoogle Scholar
  83. 83.
    Rosenecker J, Naundorf S, Gersting SW, et al. Interaction of bronchoalveolar lavage fluid with polyplexes and lipoplexes: analysing the role of proteins and glycoproteins.J Gene Med. 2003;5:49–60.PubMedGoogle Scholar
  84. 84.
    Song YK, Liu F, Liu D. Enhanced gene expression in mouse lung by prolonging the retention time of intravenously injected plasmid DNA.Gene Ther. 1998;5:1531–1537.PubMedGoogle Scholar
  85. 85.
    Ruiz FE, Clancy JP, Perricone MA, et al. A clinical inflammatory syndrome attributable to aerosolized lipid-DNA administration in cystic fibrosis.Hum Gene Ther. 2001;12:751–761.PubMedGoogle Scholar
  86. 86.
    Scheule RK, St George JA, Bagley RG, et al. Basis of pulmonary toxicity associated with cationic lipid-mediated gene transfer to the mammalian lung.Hum Gene Ther. 1997;8:689–707.PubMedCrossRefGoogle Scholar
  87. 87.
    Yew NS, Scheule RK. Toxicity of cationic lipid-DNA complexes.Adv Genet. 2005;53:189–214.PubMedCrossRefGoogle Scholar
  88. 88.
    Krieg AM. Direct immunologic activities of CpG DNA and implications for gene therapy.J Gene Med. 1999;1:56–63.PubMedGoogle Scholar
  89. 89.
    McLachlan G, Stevenson BJ, Davidson DJ, Porteous DJ. Bacterial DNA is implicated in the inflammatory response to delivery of DNA/DOTAP to mouse lungs.Gene Ther. 2000;7:384–392.PubMedGoogle Scholar
  90. 90.
    Yew NS, Wang KX, Przybylska M, et al. Contribution of plasmid DNA to inflammation in the lung after administration of cationic lipid: pDNA complexes.Hum Gene Ther. 1999;10:223–234.PubMedGoogle Scholar
  91. 91.
    Plank C, Jr, Mechtler K, Jr, Szoka FC, Jr, Wagner E. Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery.Hum Gene Ther. 1996;7:1437–1446.PubMedGoogle Scholar
  92. 92.
    Fenske DB, MacLachlan I, Cullis PR. Long-circulating vectors for the systemic delivery of genes.Curr Opin Mol Ther. 2001;3:153–158.PubMedGoogle Scholar
  93. 93.
    Song LY, Ahkong QF, Rong Q, et al. Characterization of the inhibitory effect of PEG-lipid conjugates on the intracellular delivery of plasmid and antisense DNA mediated by cationic lipid liposomes.Biochim Biophys Acta. 2002;1558:1–13.PubMedGoogle Scholar
  94. 94.
    Ambegia E, Ansell S, Cullis P, Heyes J, Palmer L, MacLachlan I. Stabilized plasmid-lipid particles containing PEG-diacylglycerols exhibit extended circulation lifetimes and tumor selective gene expression.Biochim Biophys Acta. 2005;1669:155–163.PubMedGoogle Scholar
  95. 95.
    Guo X, Jr, Szoka FC, Jr. Steric stabilization of fusogenic liposomes by a low-pH sensitive PEG-diortho ester-lipid conjugate.Bioconjug Chem. 2001;12:291–300.PubMedGoogle Scholar
  96. 96.
    Wetzer B, Byk G, Frederic M, et al. Reducible cationic lipids for gene transfer.Biochem J. 2001;356:747–756.PubMedGoogle Scholar
  97. 97.
    Huang Z, Jr, Li W, Jr, MacKay JA, Jr, Szoka F, Jr. Thiocholesterol-based lipids for ordered assembly of bioresponsive gene carriers.Mol Ther. 2005;11:409–417.PubMedGoogle Scholar
  98. 98.
    Tang F, Hughes JA. Use of dithiodiglycolic acid as a tether for cationic lipids decreases the cytotoxicity and increases transgene expression of plasmid DNAin vitro.Bioconjug Chem. 1999;10:791–796.PubMedGoogle Scholar
  99. 99.
    Singh RS, Goncalves C, Sandrin P, Pichon C, Midoux P, Chaudhuri A. On the gene delivery efficacies of pH-sensitive cationic lipids via endosomal protonation: a chemical biology investigation.Chem Biol. 2004;11:713–723.PubMedGoogle Scholar
  100. 100.
    Wu GY, Wu CH. Receptor-mediated gene delivery and expression in vivo.J Biol Chem. 1988;263:14621–14624.PubMedGoogle Scholar
  101. 101.
    Boussif O, Lezoualch F, Zanta MA, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture andin vivo: polyethylenimine.Proc Natl Acad Sci USA. 1995;92:7297–7301.PubMedGoogle Scholar
  102. 102.
    Goula D, Remy JS, Erbacher P, et al. Size, diffusibility and transfection performance of linear PEI/DNA complexes in the mouse central nervous system.Gene Ther. 1998;5:712–717.PubMedGoogle Scholar
  103. 103.
    Chemin I, Moradpour D, Wieland S, et al. Liver-directed gene transfer: a linear polyethylenimine derivative mediates highly efficient DNA delivery to primary hepatocytes in vitro and in vivo.J Viral Hepat. 1998;5:369–375.PubMedGoogle Scholar
  104. 104.
    Haensler J, Jr, Szoka FC, Jr. Polyamidoamine cascade polymers mediate efficient transfection of cells in culture.Bioconjug Chem. 1993;4:372–379.PubMedGoogle Scholar
  105. 105.
    Tang MX, Jr, Redemann CT, Jr, Szoka FC, Jr.In vitro gene delivery by degraded polyamidoamine dendrimers.Bioconjug Chem. 1996;7:703–714.PubMedGoogle Scholar
  106. 106.
    Rudolph C, Lausier J, Naundorf S, Muller RH, Rosenecker J.In vivo gene delivery to the lung using polyethylenimine and fractured polyamidoamine dendrimers.J Gene Med. 2002;2:269–278.Google Scholar
  107. 107.
    Schatzlein AG, Zinselmeyer BH, Elouzi A, et al. Preferential liver gene expression with polypropylenimine dendrimers.J Control Release. 2005;101:247–258.PubMedGoogle Scholar
  108. 108.
    Hosseinkhani H, Azzam T, Tabata Y, Domb AJ. Dextran-spermine polycation: an efficient nonviral vector forin vitro andin vivo gene transfection.Gene Ther. 2004;11:194–203.PubMedGoogle Scholar
  109. 109.
    Leong KW, Mao HQ, Truong-Le VL, Roy K, Walsh SM, August JT. DNA-polycation nanospheres as non-viral gene delivery vehicles.J Control Release. 1998;53:183–193.PubMedGoogle Scholar
  110. 110.
    Erbacher P, Zou S, Bettinger T, Steffan AM, Remy JS. Chitosanbased vector/DNA complexes for gene delivery: biophysical characteristics and transfection ability.Pharm Res. 1998;15:1332–1339.PubMedGoogle Scholar
  111. 111.
    Venkatesh S, Smith TJ. Chitosan-mediated transfection of HeLa cells.Pharm Dev Technol. 1997;2:417–418.PubMedGoogle Scholar
  112. 112.
    Lee KY, Kwon IC, Kim YH, Jo WH, Jeong SY. Preparation of chitosan self-aggregates as a gene delivery system.J Control Release. 1998;51:213–220.PubMedGoogle Scholar
  113. 113.
    Balicki D, Beutler E. Histone H2A significantly enhances in vitro DNA transfection.Mol Med. 1997;3:782–787.PubMedGoogle Scholar
  114. 114.
    Balicki D, Putnam CD, Scaria PV, Beutler E. Structure and function correlation in histone H2A peptide-mediated gene transfer.Proc Natl Acad Sci USA 2002;99:7467–7471.PubMedGoogle Scholar
  115. 115.
    Park YJ, Liang JF, Ko KS, Kim SW, Yang VC. Low molecular weight protamine as an efficient and nontoxic gene carrier:in vitro study.J Gene Med. 2003;5:700–711.PubMedGoogle Scholar
  116. 116.
    von Harpe A, Petersen H, Li Y, Kissel T. Characterization of commercially available and synthesized polyethylenimines for gene delivery.J Control Release. 2000;69:309–322.Google Scholar
  117. 117.
    Wightman L, Kircheis R, Rossler V, et al. Different behavior of branched and linear polyethylenimine for gene delivery in vitro and in vivo.J Gene Med. 2001;3:362–372.PubMedGoogle Scholar
  118. 118.
    Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T. In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis.Biomaterials. 2003;24:1121–1131.PubMedGoogle Scholar
  119. 119.
    Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T. A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity.Pharm Res. 1999;16:1273–1279.PubMedGoogle Scholar
  120. 120.
    Gosselin MA, Guo W, Lee RJ. Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine.Bioconjug Chem. 2001;12:989–994.PubMedGoogle Scholar
  121. 121.
    Forrest ML, Koerber JT, Pack DW. A degradable polyethylenimine derivative with low toxicity for highly efficient gene delivery.Bioconjug Chem. 2003;14:934–940.PubMedGoogle Scholar
  122. 122.
    Thomas M, Klibanov AM. Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells.Proc Natl Acad Sci USA. 2003;100:9138–9143.PubMedGoogle Scholar
  123. 123.
    Zhu J, Tang A, Law LP, et al. Amphiphilic core-shell nanoparticles with poly(ethylenimine) shells as potential gene delivery carriers.Bioconjug Chem. 2005;16:139–146.PubMedGoogle Scholar
  124. 124.
    Manuel WS, Zheng JI, Hornsby PJ. Transfection by polyethyleneimine-coated microspheres.J Drug Target. 2001;9:15–22.PubMedCrossRefGoogle Scholar
  125. 125.
    Thomas M, Klibanov AM. Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells.Proc Natl Acad Sci USA. 2002;99:14640–14645.PubMedGoogle Scholar
  126. 126.
    Han S, Mahato RI, Kim SW. Water-soluble lipopolymer for gene delivery.Bioconjug Chem. 2001;12:337–345.Google Scholar
  127. 127.
    Ogris M, Carlisle RC, Bettinger T, Seymour LW. Melittin enables efficient vesicular escape and enhanced nuclear access of nonviral gene delivery vectors.J Biol Chem. 2001;276:47550–47555.PubMedGoogle Scholar
  128. 128.
    Boeckle S, Fahrmeir J, Roedl W, Ogris M, Wagner E. Melittin analogs with high lytic activity at endosomal pH enhance transfection with purified targeted PEI polyplexes.J Control Release. 2006;112:240–248.PubMedGoogle Scholar
  129. 129.
    Kichler A. Gene transfer with modified polyethylenimines.J Gene Med. 2004;6:S3–10.Google Scholar
  130. 130.
    Goula D, Benoist C, Mantero S, Merlo G, Levi G, Demeneix BA. Polyethylenimine-based intravenous delivery of transgenes to mouse lung.Gene Ther. 1998;5:1291–1295.PubMedGoogle Scholar
  131. 131.
    Sweeney P, Karashima T, Ishikura H, et al. Efficient therapeutic gene delivery after systemic administration of a novel polyethylenimine/DNA vector in an orthotopic bladder cancer model.Cancer Res. 2003;63:4017–4020.PubMedGoogle Scholar
  132. 132.
    Wagner E. Strategies to improve DNA polyplexes forin vivo gene transfer: will “artificial viruses” be the answer?Pharm Res. 2004;21:8–14.PubMedGoogle Scholar
  133. 133.
    Gautam A, Densmore CL, Xu B, Waldrep JC. Enhanced gene expression in mouse lung after PEI-DNA aerosol delivery.Mol Ther. 2000;2:63–70.PubMedGoogle Scholar
  134. 134.
    Akinc A, Anderson DG, Lynn DM, Langer R. Synthesis of poly(beta-amino ester)s optimized for highly effective gene delivery.Bioconjug Chem. 2003;14:979–988.PubMedGoogle Scholar
  135. 135.
    Lim YB, Kim SM, Suh H, Park JS. Biodegradable, endosome disruptive, and cationic network-type polymer as a highly efficient and nontoxic gene delivery carrier.Bioconjug Chem. 2002;13:952–957.PubMedGoogle Scholar
  136. 136.
    Lim YB, Han SO, Kong HU, et al. Biodegradable polyester, poly[alpha-(4-aminobutyl)-L-glycolic acid], as a non-toxic gene carrier.Pharm Res. 2000;17:811–816.PubMedGoogle Scholar
  137. 137.
    Sonawane ND, Jr, Szoka FC, Jr, Verkman AS. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes.J Biol Chem. 2003;278:44826–44831.PubMedGoogle Scholar
  138. 138.
    Rudolph C, Plank C, Lausier J, Schillinger U, Muller RH, Rosenecker J. Oligomers of the arginine-rich motif of the HIV-1 TAT protein are capable of transferring plasmid DNA into cells.J Biol Chem. 2003;278:11411–11418.PubMedGoogle Scholar
  139. 139.
    Avrameas A, Ternynck T, Nato F, Buttin G, Avrameas S. Polyreactive anti-DNA monoclonal antibodies and a derived peptide as vectors for the intracytoplasmic and intranuclear translocation of macromolecules.Proc Natl Acad Sci USA. 1998;95:5601–5606.PubMedGoogle Scholar
  140. 140.
    Gao X, Huang L. Potentiation of cationic liposome-mediated gene delivery by polycations.Biochemistry 1996;35:1027–1036.PubMedGoogle Scholar
  141. 141.
    Sorgi FL, Bhattacharya S, Huang L. Protamine sulfate enhances lipid-mediated gene transfer.Gene Ther. 1997;4:961–968.PubMedGoogle Scholar
  142. 142.
    Lee RJ, Huang L. Folate-targeted, anionic liposome-entrapped polylysine-condensed DNA for tumor cell-specific gene transfer.J Biol Chem. 1996;271:8481–8487.PubMedGoogle Scholar
  143. 143.
    Lee LK, Williams CL, Devore D, Roth CM. Poly(propylacrylic acid) enhances cationic lipid-mediated delivery of antisense oligonucleotides.Biomacromolecules. 2006;7:1502–1508.PubMedGoogle Scholar
  144. 144.
    Li S, Huang L.In vivo gene transfer via intravenous administration of cationic lipid-protamine-DNA (LPD) complexes.Gene Ther. 1997;4:891–900.PubMedGoogle Scholar
  145. 145.
    Murphy EA, Waring AJ, Haynes SM, Longmuir KJ. Compaction of DNA in an anionic micelle environment followed by assembly into phosphatidylcholine liposomes.Nucleic Acids Res. 2000;28:2986–2992.PubMedGoogle Scholar
  146. 146.
    Murphy EA, Waring AJ, Murphy JC, Willson RC, Longmuir KJ. Development of an effective gene delivery system: a study of complexes composed of a peptide-based amphiphilic DNA compaction agent and phospholipid.Nucleic Acids Res. 2001;29:3694–3704.PubMedGoogle Scholar
  147. 147.
    Longmuir KJ, Haynes SM, Dickinson ME, Murphy JC, Willson RC, Waring AJ. Optimization of a peptide/non-cationic lipid gene delivery system for effective microinjection into chicken embryo in vivo.Mol Ther. 2001;4:66–74.PubMedGoogle Scholar
  148. 148.
    Maitra A. Calcium phosphate nanoparticles: second-generation nonviral vectors in gene therapy.Expert Rev Mol Diagn. 2005;5:893–905.PubMedGoogle Scholar
  149. 149.
    Megeed Z, Jr, Haider M, Jr, Li D, Jr, O'Malley BW, Jr, Cappello J, Ghandehari H.In vitro andin vivo evaluation of recombinant silkelastinlike hydrogels for cancer gene therapy.J Control Release. 2004;94:433–445.PubMedGoogle Scholar
  150. 150.
    Wagner E. Application of membrane-active peptides for nonviral gene delivery.Adv Drug Deliv Rev. 1999;38:279–289.PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, School of PharmacyUniversity of PittsburghPittsburgh

Personalised recommendations