References and Notes

  • 1
    U.S. National Institutes of Health, (accessed Mar 31, 2006).
  • 2
    Journal of Gene Medicine, Gene Therapy Clinical Trials Worldwide. (accessed Dec 31, 2006).
  • 3
    Richardson, T. P.; Murphy, W. L.; Mooney, D. J. Polymeric delivery of proteins and plasmid DNA for tissue engineering and gene therapy. Crit. Rev. Eukaryotic Gene Expression 2001, 11, 4758.
  • 4
    Akinc, A.; Anderson, D. G.; Lynn, D. M.; Langer, R. Synthesis of poly(beta-amino ester)s optimized for highly effective gene delivery. Bioconjugate Chem. 2003, 14, 979988.
  • 5
    Lechardeur, D.; Lukacs, G. L. Intracellular barriers to non-viral gene transfer. Curr. Gene Ther. 2002, 2, 183194.
  • 6
    de Semir, D.; Petriz, J.; Avinyo, A.; Larriba, S.; Nunes, V.; Casals, T.; Estivill, X.; Aran, J. M. Non-viral vector-mediated uptake, distribution, and stability of chimeraplasts in human airway epithelial cells. J. Gene Med. 2002, 4, 308322.
  • 7
    Gao, S.; Chen, J.; Dong, L.; Ding, Z.; Yang, Y. H.; Zhang, J. Targeting delivery of oligonucleotide and plasmid DNA to hepatocyte via galactosylated chitosan vector. Eur. J. Pharm. Biopharm. 2005, 60, 327334.
  • 8
    Feng, M.; Lee, D.; Li, P. Intracellular uptake and release of poly(ethyleneimine)-co-poly(methyl methacrylate) nanoparticle/pDNA complexes for gene delivery. Int. J. Pharm. 2006, 311, 209214.
  • 9
    Huang, M.; Fong, C. W.; Khor, E.; Lim, L. Y. Transfection efficiency of chitosan vectors: effect of polymer molecular weight and degree of deacetylation. J. Controlled Release 2005, 106, 391406.
  • 10
    Hashimoto, M.; Morimoto, M.; Saimoto, H.; Shigemasa, Y.; Sato, T. Lactosylated chitosan for DNA delivery into hepatocytes: the effect of lactosylation on the physicochemical properties and intracellular trafficking of pDNA/chitosan complexes. Bioconjugate Chem. 2006, 17, 309316.
  • 11
    Kaul, G.; Amiji, M. Cellular interactions and in vitro DNA transfection studies with poly(ethylene glycol)-modified gelatin nanoparticles. J. Pharm. Sci. 2005, 94, 184198.
  • 12
    Mao, H. Q.; Roy, K.; Troung, L.; Janes, K. A.; Lin, K. Y.; Wang, Y.; August, J. T.; Leong, K. W. Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J. Controlled Release 2001, 70, 399421.
  • 13
    Akbuga, J.; Ozbas-Turan, S.; Erdogan, N. Plasmid-DNA loaded chitosan microspheres for in vitro IL-2 expression. Eur. J. Pharm. Biopharm. 2004, 58, 501507.
  • 14
    Dastan, T.; Turan, K. In vitro characterization and delivery of chitosan-DNA microparticles into mammalian cells. J. Pharm. Pharm. Sci. 2004, 7, 205214.
  • 15
    Itaka, K.; Harada, A.; Yamasaki, Y.; Nakamura, K.; Kawaguchi, H. Kataoka, K. In situ single cell observation by fluorescence resonance energy transfer reveals fast intra-cytoplasmic delivery and easy release of plasmid DNA complexed with linear polyethylenimine. J. Gene Med. 2004, 6, 7684.
  • 16
    Lechardeur, D.; Verkman, A. S.; Lukacs, G. L. Intracellular routing of plasmid DNA during non-viral gene transfer. Adv. Drug Delivery Rev. 2005, 57, 755767.
  • 17
    Medina-Kauwe, L. K.; Xie, J. ; Hamm-Alvarez, S. Intracellular trafficking of nonviral vectors. Gene Ther. 2005, 12, 17341751.
  • 18
    Hu, Y.; Jin, Y.; Xia, Y. The characterization of cationic fusogenic liposomes mediated antisense oligonucleotides into HeLa cells. Drug Dev. Ind. Pharm. 2004, 30, 135141.
  • 19
    Kunisawa, J.; Masuda, T.; Katayama, K.; Yoshikawa, T.; Tsutsumi, Y.; Akashi, M.; Mayumi, T.; Nakagawa, S. Fusogenic liposome delivers encapsulated nanoparticles for cytosolic controlled gene release. J. Controlled Release 2005, 105, 344353.
  • 20
    Huang, M.; Ma, Z.; Khor, E.; Lim, L. Y. Uptake of FITC-chitosan nanoparticles by A549 cells. Pharm. Res. 2002, 19, 14881494.
  • 21
    Panyam, J.; Labhasetwar, V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Delivery Rev. 2003, 55, 329347.
  • 22
    Colin, M.; Maurice, M.; Trugnan, G.; Kornprobst, M.; Harbottle, R.P.; Knight, A.; Cooper, R. G.; Miller, A. D.; Capeau, J.; Coutelle, C.; Brahimi-Horn, M. C. Cell delivery, intracellular trafficking and expression of an integrin-mediated gene transfer vector in tracheal epithelial cells. Gene Ther. 2000, 7, 139152.
  • 23
    Rejman, J.; Bragonzi, A.; Conese, M. Role of clathrin- and caveolae-mediated endocytosis in gene transfer mediated by lipo- and polyplexes. Mol. Ther. 2005, 12, 468474.
  • 24
    Manunta, M.; Tan, P. H.; Sagoo, P.; Kashefi, K.; George, A. J. Gene delivery by dendrimers operates via a cholesterol dependent pathway. Nucleic Acids Res. 2004, 32, 27302739.
  • 25
    Johannes, L.; Lamaze, C. Clathrin-dependent or not: is it still the question? Traffic 2002, 3, 443451.
  • 26
    Conner, S. D.; Schmid, S. L. Regulated portals of entry into the cell. Nature 2003, 422, 3744.
  • 27
    Kessner, S.; Krause, A.; Rothe, U.; Bendas, G. Investigation of the cellular uptake of E-Selectin-targeted immunoliposomes by activated human endothelial cells. Biochim. Biophys. Acta 2001, 1514, 177190.
  • 28
    Huang, M.; Khor, E.; Lim, L. Y. Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation. Pharm. Res. 2004, 21, 344353.
  • 29
    Ma, Z.; Lim, L. Y. Uptake of chitosan and associated insulin in Caco-2 cell monolayers: a comparison between chitosan molecules and chitosan nanoparticles. Pharm. Res. 2003, 20, 18121819.
  • 30
    Goncalves, C.; Mennesson, E.; Fuchs, R.; Gorvel, J. P.; Midoux, P. Pichon, C. Macropinocytosis of polyplexes and recycling of plasmid via the clathrin-dependent pathway impair the transfection efficiency of human hepatocarcinoma cells. Mol. Ther. 2004, 10, 373385.
  • 31
    Rejman, J.; Oberle, V.; Zuhorn, I. S.; Hoekstra, D. Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem. J. 2004, 377, 159169.
  • 32
    Huth, U.; Wieschollek, A.; Garini, Y.; Schubert, R. ; Peschka-Suss, R. Fourier transformed spectral bio-imaging for studying the intracellular fate of liposomes. Cytometry A 2004, 57, 1021.
  • 33
    Zuhorn, I. S.; Kalicharan, R.; Hoekstra, D. Lipoplex-mediated transfection of mammalian cells occurs through the cholesterol-dependent clathrin-mediated pathway of endocytosis. J. Biol. Chem. 2002, 277, 1802118028.
  • 34
    Bartlett, J. S.; Wilcher, R.; Samulski, R. J. Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors. J. Virol. 2000, 74, 27772785.
  • 35
    Douar, A. M.; Poulard, K.; Stockholm, D.; Danos, O. Intracellular trafficking of adeno-associated virus vectors: routing to the late endosomal compartment and proteasome degradation. J. Virol. 2001, 75, 18241833.
  • 36
    Daecke, J.; Fackler, O. T.; Dittmar, M. T.; Krausslich, H. G. Involvement of clathrin-mediated endocytosis in human immunodeficiency virus type 1 entry. J. Virol. 2005, 79, 15811594.
  • 37
    Vendeville, A.; Rayne, F.; Bonhoure, A.; Bettache, N.; Montcourrier, P.; Beaumelle, B. HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses. Mol. Biol. Cell 2004, 15, 23472360.
  • 38
    Medina-Kauwe, L. K. Endocytosis of adenovirus and adenovirus capsid proteins. Adv. Drug Delivery Rev. 2003, 55, 14851496.
  • 39
    Chung, S. K.; Kim, J. Y.; Kim, I. B.; Park, S. I.; Paek, K. H.; Nam, J. H. Internalization and trafficking mechanisms of coxsackievirus B3 in HeLa cells. Virology 2005, 333, 3140.
  • 40
    Meertens, L.; Bertaux, C.; Dragic, T. Hepatitis C virus entry requires a critical postinternalization step and delivery to early endosomes via clathrin-coated vesicles. J. Virol. 2006, 80, 1157111578.
  • 41
    Cooper, A.; Shaul, Y. Clathrin-mediated endocytosis and lysosomal cleavage of hepatitis B virus capsid-like core particles. J. Biol. Chem. 2006, 281, 1656316569.
  • 42
    Mo, Y.; Lim, L. Y. Mechanistic study of the uptake of wheat germ agglutinin-conjugated PLGA nanoparticles by A549 cells. J. Pharm. Sci. 2004, 93, 2028.
  • 43
    Fittipaldi, A.; Ferrari, A.; Zoppe, M.; Arcangeli, C.; Pellegrini, V.; Beltram, F.; Giacca, M. Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins. J. Biol. Chem. 2003, 278, 3414134149.
  • 44
    Basner-Tschakarjan, E.; Mirmohammadsadegh, A.; Baer, A.; Hengge, U. R. Uptake and trafficking of DNA in keratinocytes: evidence for DNA-binding proteins. Gene Ther. 2004, 11, 765774.
  • 45
    Qaddoumi, M. G.; Gukasyan, H. J.; Davda, J.; Labhasetwar, V.; Kim, K. J.; Lee, V. H. Clathrin and caveolin-1 expression in primary pigmented rabbit conjunctival epithelial cells: role in PLGA nanoparticle endocytosis. Mol. Vision 2003, 9, 559568.
  • 46
    Brisson, M.; Tseng, W. C.; Almonte, C.; Watkins, S.; Huang, L. Subcellular trafficking of the cytoplasmic expression system. Hum. Gene Ther. 1999, 10, 26012613.
  • 47
    Nakase, I.; Niwa, M.; Takeuchi, T.; Sonomura, K.; Kawabata, N.; Koike, Y.; Takehashi, M.; Tanaka, S.; Ueda, K.; Simpson, J.C.; Jones, A. T.; Sugiura, Y.; Futaki, S. Cellular uptake of arginine-rich peptides: roles for macropinocytosis and actin rearrangement. Mol. Ther. 2004, 10, 10111022.
  • 48
    Wadia, J. S.; Stan, R. V.; Dowdy, S. F. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat. Med. 2004, 10, 310315.
  • 49
    Pouton, C. W.; Lucas, P.; Thomas, B. J.; Uduehi, A. N.; Milroy, D.A.; Moss, S. H. Polycation-DNA complexes for gene delivery: a comparison of the biopharmaceutical properties of cationic polypeptides and cationic lipids. J. Controlled Release 1998, 53, 289299.
  • 50
    Simoes, S.; Slepushkin, V.; Pires, P.; Gaspar, R.; de Lima, M. P.; Duzgunes, N. Mechanisms of gene transfer mediated by lipoplexes associated with targeting ligands or pH-sensitive peptides. Gene Ther. 1999, 6, 17981807.
  • 51
    Prabha, S.; Zhou, W. Z.; Panyam, J.; Labhasetwar, V. Size-dependency of nanoparticle-mediated gene transfection: studies with fractionated nanoparticles. Int. J. Pharm. 2002, 244, 105115.
  • 52
    Godbey, W. T.; Mikos, A. G. Recent progress in gene delivery using non-viral transfer complexes. J. Controlled Release 2001, 72, 115125.
  • 53
    Akita, H.; Ito, R.; Khalil, I. A.; Futaki, S.; Harashima, H. Quantitative three-dimensional analysis of the intracellular trafficking of plasmid DNA transfected by a nonviral gene delivery system using confocal laser scanning microscopy. Mol. Ther. 2004, 9, 443451.
  • 54
    Laurent, N.; Wattiaux-De, C. S.; Mihaylova, E.; Leontieva, E.; Warnier-Pirotte, M. T.; Wattiaux, R.; Jadot, M. Uptake by rat liver and intracellular fate of plasmid DNA complexed with poly-l-lysine or poly-d-lysine. FEBS Lett. 1999, 443, 6165.
  • 55
    Cho, Y. W.; Kim, J. D.; Park, K. Polycation gene delivery systems: escape from endosomes to cytosol. J. Pharm. Pharmacol. 2003, 55, 721734.
  • 56
    Davda, J.; Labhasetwar, V. Characterization of nanoparticle uptake by endothelial cells. Int. J. Pharm. 2002, 233, 5159.
  • 57
    Popielarski, S. R.; Hu-Lieskovan, S.; French, S. W.; Triche, T.J.; Davis, M. E. A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 2. In vitro and in vivo uptake results. Bioconjugate Chem. 2005, 16, 10711080.
  • 58
    Qaddoumi, M. G.; Ueda, H.; Yang, J.; Davda, J.; Labhasetwar, V.; Lee, V. H. The characteristics and mechanisms of uptake of PLGA nanoparticles in rabbit conjunctival epithelial cell layers. Pharm. Res. 2004, 21, 641648.
  • 59
    Harush-Frenkel, O.; Debotton, N.; Benita, S.; Altschuler, Y. Targeting of nanoparticles to the clathrin-mediated endocytic pathway. Biochem. Biophys. Res. Commun. 2007, 353, 2632.
  • 60
    Farrell, L. L.; Pepin, J.; Kucharski, C.; Lin, X.; Xu, Z.; Uludag, H. A comparison of the effectiveness of cationic polymers poly-l-lysine (PLL) and polyethylenimine (PEI) for non-viral delivery of plasmid DNA to bone marrow stromal cells (BMSC). Eur. J. Pharm. Biopharm. 2007, 65, 388397.
  • 61
    Mishra, S.; Webster, P.; Davis, M. E. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles. Eur. J. Cell Biol. 2004, 83, 97111.
  • 62
    Hsu, C.; Uludag, H. Effect of size and topology of DNA molecules on intracellular delivery with non-viral gene carriers. BMC Biotechnol. 2007, submitted.
  • 63
    Dailey, L. A.; Kleemann, E.; Merdan, T.; Petersen, H.; Schmehl, T.; Gessler, T.; Hanze, J.; Seeger, W.; Kissel, T. Modified polyethylenimines as non viral gene delivery systems for aerosol therapy: effects of nebulization on cellular uptake and transfection efficiency. J. Controlled Release 2004, 100, 425436.
  • 64
    Douglas, K. L.; Piccirillo, C. A.; Tabrizian, M. Effects of alginate inclusion on the vector properties of chitosan-based nanoparticles. J. Controlled Release 2006, 115, 354361.
  • 65
    Gianni, T.; Campadelli-Fiume, G.; Menotti, L. Entry of herpes simplex virus mediated by chimeric forms of nectin1 retargeted to endosomes or to lipid rafts occurs through acidic endosomes. J. Virol. 2004, 78, 1226812276.
  • 66
    Hama, S.; Akita, H.; Ito, R.; Mizuguchi, H.; Hayakawa, T. ; Harashima, H. Quantitative comparison of intracellular trafficking and nuclear transcription between adenoviral and lipoplex systems. Mol. Ther. 2006, 13, 786794.
  • 67
    Moritz, S.; Colin, M.; Keller, M.; Klonjkowski, B.; Capeau, J.; Coutelle, C.; Chroboczek, J.; Brahimi-Horn, M. C. Gene transfer by adenovirus-mimetic peptides in the presence of a cationic lipid and/or adenovirus. Analysis of the contribution of the viral and nonviral components. Arch. Virol. 2003, 148, 118.
  • 68
    Bieber, T.; Meissner, W.; Kostin, S.; Niemann, A.; Elsasser, H. P. Intracellular route and transcriptional competence of polyethylenimine-DNA complexes. J. Controlled Release 2002, 82, 441454.
  • 69
    Hoekstra, D.; Rejman, J.; Wasungu, L.; Shi, F.; Zuhorn, I. Gene delivery by cationic lipids: in and out of an endosome. Biochem. Soc. Trans. 2007, 35, 6871.
  • 70
    Wattiaux, R.; Laurent, N.; Wattiaux-De, C. S.; Jadot, M. Endosomes, lysosomes: their implication in gene transfer. Adv. Drug Delivery Rev. 2000, 41, 201208.
  • 71
    Godbey, W. T.; Wu, K. K.; Mikos, A. G. Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 51775181.
  • 72
    Godbey, W. T.; Barry, M. A.; Saggau, P.; Wu, K. K.; Mikos, A. G. Poly(ethylenimine)-mediated transfection: a new paradigm for gene delivery. J. Biomed. Mater. Res. 2000, 51, 321328.
  • 73
    Panyam, J.; Zhou, W. Z.; Prabha, S.; Sahoo, S. K.; Labhasetwar, V. Rapid endo-lysosomal escape of poly(dl-lactide- co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J. 2002, 16, 12171226.
  • 74
    Cornelis, S.; Vandenbranden, M.; Ruysschaert, J. M.; Elouahabi, A. Role of intracellular cationic liposome-DNA complex dissociation in transfection mediated by cationic lipids. DNA Cell Biol. 2002, 21, 9197.
  • 75
    von, G. K.; Sanders, N. N.; Vandenbroucke, R.; De Smedt, S. C.; Wagner, E.; Ogris, M. The internalization route resulting in successful gene expression depends on both cell line and polyethylenimine polyplex type. Mol. Ther. 2006, 14, 745753.
  • 76
    van der Aa, M. A.; Huth, U. S.; Hafele, S. Y.; Schubert, R.; Oosting, R. S.; Mastrobattista, E.; Hennink, W. E.; Peschka-Suss, R.; Koning, G. A.; Crommelin, D. J. Cellular uptake of cationic polymer-DNA complexes via caveolae plays a pivotal role in gene transfection in COS-7 cells. Pharm. Res. 2007, 24, 15901598.
  • 77
    Ding, W.; Zhang, L.; Yan, Z.; Engelhardt, J. F. Intracellular trafficking of adeno-associated viral vectors. Gene Ther. 2005, 12, 873880.
  • 78
    Hansen, J.; Qing, K.; Srivastava, A. Adeno-associated virus type 2-mediated gene transfer: altered endocytic processing enhances transduction efficiency in murine fibroblasts. J. Virol. 2001, 75, 40804090.
  • 79
    Rentsendorj, A.; Xie, J.; MacVeigh, M.; Agadjanian, H.; Bass, S.; Kim, D. H.; Rossi, J.; Hamm-Alvarez, S. F. ; Medina-Kauwe, L. K. Typical and atypical trafficking pathways of Ad5 penton base recombinant protein: implications for gene transfer. Gene Ther. 2006, 13, 821836.
  • 80
    Xu, Y.; Szoka, F. C. , Jr. Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 1996, 35, 56165623.
  • 81
    Cho, Y. W.; Kim, J. D.; Park, K. Polycation gene delivery systems: escape from endosomes to cytosol. J. Pharm. Pharmacol. 2003, 55, 721734.
  • 82
    Fang, N.; Chan, V.; Mao, H. Q.; Leong, K. W. Interactions of phospholipid bilayer with chitosan: effect of molecular weight and pH. Biomacromolecules 2001, 2, 11611168.
  • 83
    Kichler, A.; Leborgne, C.; Danos, O.; Bechinger, B. Characterization of the gene transfer process mediated by histidine-rich peptides. J. Mol. Med. 2007, 85, 191201.
  • 84
    Colin, M.; Renaut, L.; Mailly, L.; D'Halluin, J. C. Factors involved in the sensitivity of different hematopoietic cell lines to infection by subgroup C adenovirus: implication for gene therapy of human lymphocytic malignancies. Virology 2004, 320, 2339.
  • 85
    Kamiya, H.; Tsuchiya, H.; Yamazaki, J.; Harashima, H. Intracellular trafficking and transgene expression of viral and non-viral gene vectors. Adv. Drug Delivery Rev. 2001, 52, 153164.
  • 86
    Yamagata, M.; Kawano, T.; Shiba, K.; Mori, T.; Katayama, Y.; Niidome, T. Structural advantage of dendritic poly(l-lysine) for gene delivery into cells. Bioorg. Med. Chem. 2007, 15, 526532.
  • 87
    Boeckle, S.; von, G. K.; van der, P. S.; Culmsee, C.; Wagner, E. Ogris, M.; Purification of polyethylenimine polyplexes highlights the role of free polycations in gene transfer. J. Gene Med. 2004, 6, 11021111.
  • 88
    Ishii, T.; Okahata, Y.; Sato, T. Mechanism of cell transfection with plasmid/chitosan complexes. Biochim. Biophys. Acta 2001, 1514, 5164.
  • 89
    Ogris, M.; Carlisle, R. C.; Bettinger, T.; Seymour, L. W. Melittin enables efficient vesicular escape and enhanced nuclear access of nonviral gene delivery vectors. J. Biol. Chem. 2001, 276, 4755047555.
  • 90
    Kakudo, T.; Chaki, S.; Futaki, S.; Nakase, I.; Akaji, K.; Kawakami, T.; Maruyama, K.; Kamiya, H.; Harashima, H. Transferrin-modified liposomes equipped with a pH-sensitive fusogenic peptide: an artificial viral-like delivery system. Biochemistry 2004, 43, 56185628.
  • 91
    Abbasi, M.; Uludag, H.; Incani, V.; Olson, C.; Lin, X.; Clements, B.A.; Rutkowski, D.; Ghahary, A.; Weinfeld, M. Palmitic acid-modified poly-l-lysine for non-viral delivery of plasmid DNA to skin fibroblasts. Biomacromolecules 2007, 8, 10591063.
  • 92
    Curiel, D. T.; Agarwal, S.; Wagner, E.; Cotten, M. Adenovirus enhancement of transferrin-polylysine-mediated gene delivery. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 88508854.
  • 93
    Prabha, S.; Labhasetwar, V. Critical determinants in PLGA/PLA nanoparticle-mediated gene expression. Pharm. Res. 2004, 21, 354364.
  • 94
    Lechardeur, D.; Lukacs, G. L. Nucleocytoplasmic transport of plasmid DNA: a perilous journey from the cytoplasm to the nucleus. Hum. Gene Ther. 2006, 17, 882889.
  • 95
    Dowty, M. E.; Williams, P.; Zhang, G.; Hagstrom, J. E.; Wolff, J. A. Plasmid DNA entry into postmitotic nuclei of primary rat myotubes. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 45724576.
  • 96
    Holmes, A. R.; Dohrman, A. F.; Ellison, A. R.; Goncz, K. K.; Gruenert, D. C. Intracellular compartmentalization of DNA fragments in cultured airway epithelial cells mediated by cationic lipids. Pharm. Res. 1999, 16, 10201025.
  • 97
    Dauty, E.; Verkman, A. S. Actin cytoskeleton as the principal determinant of size-dependent DNA mobility in cytoplasm: a new barrier for non-viral gene delivery. J. Biol. Chem. 2005, 280, 78237828.
  • 98
    Geiger, R. C.; Taylor, W.; Glucksberg, M. R.; Dean, D. A. Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer. Gene Ther. 2006, 13, 725731.
  • 99
    Lukacs, G. L.; Haggie, P.; Seksek, O.; Lechardeur, D.; Freedman, N.; Verkman, A. S. Size-dependent DNA mobility in cytoplasm and nucleus. J. Biol. Chem. 2000, 275, 16251629.
  • 100
    Remaut, K.; Sanders, N. N.; Fayazpour, F.; Demeester, J.; De Smedt, S. C. Influence of plasmid DNA topology on the transfection properties of DOTAP/DOPE lipoplexes. J. Controlled Release 2006, 115, 335343.
  • 101
    Zauner, W.; Brunner, S.; Buschle, M.; Ogris, M.; Wagner, E. Differential behaviour of lipid based and polycation based gene transfer systems in transfecting primary human fibroblasts: a potential role of polylysine in nuclear transport. Biochim. Biophys. Acta 1999, 1428, 5767.
  • 102
    Colin, M.; Moritz, S.; Fontanges, P.; Kornprobst, M.; Delouis, C.; Keller, M.; Miller, A. D.; Capeau, J.; Coutelle, C.; Brahimi-Horn, M. C. The nuclear pore complex is involved in nuclear transfer of plasmid DNA condensed with an oligolysine-RGD peptide containing nuclear localisation properties. Gene Ther. 2001, 8, 16431653.
  • 103
    Liu, G.; Li, D.; Pasumarthy, M. K.; Kowalczyk, T. H.; Gedeon, C.R.; Hyatt, S. L.; Payne, J. M.; Miller, T. J.; Brunovskis, P.; Fink, T.L.; Muhammad, O.; Moen, R. C.; Hanson, R. W.; Cooper, M. J. Nanoparticles of compacted DNA transfect postmitotic cells. J. Biol. Chem. 2003, 278, 3257832586.
  • 104
    Godbey, W. T.; Wu, K. K.; Mikos, A. G. Poly(ethylenimine) and its role in gene delivery. J. Controlled Release 1999, 60, 149160.
  • 105
    Ludtke, J. J.; Sebestyen, M. G.; Wolff, J. A. The effect of cell division on the cellular dynamics of microinjected DNA and dextran. Mol. Ther. 2002, 5, 579588.
  • 106
    Escriou, V.; Carriere, M.; Bussone, F.; Wils, P.; Scherman, D. Critical assessment of the nuclear import of plasmid during cationic lipid-mediated gene transfer. J. Gene Med. 2001, 3, 179187.
  • 107
    Mannisto, M.; Ronkko, S.; Matto, M.; Honkakoski, P.; Hyttinen, M.; Pelkonen, J.; Urtti, A. The role of cell cycle on polyplex-mediated gene transfer into a retinal pigment epithelial cell line. J. Gene Med. 2005, 7, 466476.
  • 108
    Brunner, S.; Furtbauer, E.; Sauer, T.; Kursa, M.; Wagner, E. Overcoming the nuclear barrier: cell cycle independent nonviral gene transfer with linear polyethylenimine or electroporation. Mol. Ther. 2002, 5, 8086.
  • 109
    Grosse, S.; Thevenot, G.; Monsigny, M.; Fajac, I. Which mechanism for nuclear import of plasmid DNA complexed with polyethylenimine derivatives? J. Gene Med. 2006, 8, 845851.
  • 110
    Pollard, H.; Remy, J. S.; Loussouarn, G.; Demolombe, S.; Behr, J.P. ; Escande, D. Polyethylenimine but not cationic lipids promotes transgene delivery to the nucleus in mammalian cells. J. Biol. Chem. 1998, 273, 75077511.
  • 111
    Wilson, G. L.; Dean, B. S.; Wang, G.; Dean, D. A. Nuclear import of plasmid DNA in digitonin-permeabilized cells requires both cytoplasmic factors and specific DNA sequences. J. Biol. Chem. 1999, 274, 2202522032.
  • 112
    Zanta, M. A.; Belguise-Valladier, P.; Behr, J. P. Gene delivery: a single nuclear localization signal peptide is sufficient to carry DNA to the cell nucleus. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 9196.
  • 113
    Ludtke, J. J.; Zhang, G.; Sebestyen, M. G.; Wolff, J. A. A nuclear localization signal can enhance both the nuclear transport and expression of 1 kb DNA. J. Cell Sci. 1999, 112 (Pt 12), 20332041.
  • 114
    Branden, L. J.; Mohamed, A. J.; Smith, C. I. A peptide nucleic acid-nuclear localization signal fusion that mediates nuclear transport of DNA. Nat. Biotechnol. 1999, 17, 784787.
  • 115
    Chen, J.; Stickles, R. J.; Daichendt, K. A. Galactosylated histone-mediated gene transfer and expression. Hum. Gene Ther. 1994, 5, 429435.
  • 116
    Carlisle, R. C.; Bettinger, T.; Ogris, M.; Hale, S.; Mautner, V.; Seymour, L. W. Adenovirus hexon protein enhances nuclear delivery and increases transgene expression of polyethylenimine/plasmid DNA vectors. Mol. Ther. 2001, 4, 473483.
  • 117
    Klink, D.; Yu, Q. C.; Glick, M. C.; Scanlin, T. Lactosylated poly-l-lysine targets a potential lactose receptor in cystic fibrosis and non-cystic fibrosis airway epithelial cells. Mol. Ther. 2003, 7, 7380.
  • 118
    Mesika, A.; Kiss, V.; Brumfeld, V.; Ghosh, G.; Reich, Z. Enhanced intracellular mobility and nuclear accumulation of DNA plasmids associated with a karyophilic protein. Hum. Gene Ther. 2005, 16, 200208.
  • 119
    Suvanasuthi, S.; Tamai, K.; Kaneda, Y. Rapid transport of plasmid DNA into the nucleolus via actin depolymerization using the HVJ envelope vector. J. Gene Med. 2007, 9, 5562.
  • 120
    Bremner, K. H.; Seymour, L. W.; Logan, A.; Read, M. L. Factors influencing the ability of nuclear localization sequence peptides to enhance nonviral gene delivery. Bioconjugate Chem. 2004, 15, 152161.
  • 121
    Varga, C. M.; Tedford, N. C.; Thomas, M.; Klibanov, A. M.; Griffith, L. G.; Lauffenburger, D. A. Quantitative comparison of polyethylenimine formulations and adenoviral vectors in terms of intracellular gene delivery processes. Gene Ther. 2005, 12, 10231032.
  • 122
    Liang, D. C.; Liu, W. G.; Zuo, A. J.; Sun, S. J.; Cheng, N.; Guo, G.; Zhang, J. Y.; De, Y. K. Pre-deliver chitosanase to cells: a novel strategy to improve gene expression by endocellular degradation-induced vector unpacking. Int. J. Pharm. 2006, 314, 6371.
  • 123
    Ahmad, A.; Evans, H. M.; Ewert, K.; George, C. X.; Samuel, C.E.; Safinya, C. R. New multivalent cationic lipids reveal bell curve for transfection efficiency versus membrane charge density: lipid-DNA complexes for gene delivery. J. Gene Med. 2005, 7, 739748.
  • 124
    Saito, Y.; Kawakami, S.; Yabe, Y.; Yamashita, F.; Hashida, M. Intracellular trafficking is the important process that determines the optimal charge ratio on transfection by galactosylated lipoplex in HEPG2 cells. Biol. Pharm. Bull. 2006, 29, 19861990.
  • 125
    Bertschinger, M.; Backliwal, G.; Schertenleib, A.; Jordan, M.; Hacker, D. L.; Wurm, F. M. Disassembly of polyethylenimine-DNA particles in vitro: implications for polyethylenimine-mediated DNA delivery. J. Controlled Release 2006, 116, 96104.
  • 126
    Clamme, J. P.; Krishnamoorthy, G.; Mely, Y. Intracellular dynamics of the gene delivery vehicle polyethylenimine during transfection: investigation by two-photon fluorescence correlation spectroscopy. Biochim. Biophys. Acta 2003, 1617, 5261.
  • 127
    Masuda, T.; Akita, H.; Harashima, H. Evaluation of nuclear transfer and transcription of plasmid DNA condensed with protamine by microinjection: the use of a nuclear transfer score. FEBS Lett. 2005, 579, 21432148.
  • 128
    Fredman, J. N.; Engler, J. A. Adenovirus precursor to terminal protein interacts with the nuclear matrix in vivo and in vitro. J. Virol. 1993, 67, 33843395.