5 Conclusions
The physicochemical features of the polyplexes are extremely important for designing effective non-viral carriers. Recently, several new systems have been described but are not well tested with respect to intracellular trafficking and transcription event. For example, non-condensing polyplexes are advantageous for transcription but, at the same time, are disadvantageous for nuclease digestion of DNA. In order to design and develop, new effective carriers, each step of intracellular trafficking route should be analyzed quantitatively.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
Keywords
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
Ahn CH, Chae SY, Bae YH, Kim SW (2002) Biodegradable poly(ethylenimine) for plasmid DNA delivery. J Control Release 80:273–282
Arigita C, Zuidam NJ, Crommelin DJ, Hennink WE (1999) Association and dissociation characteristics of polymer/DNA complexes used for gene delivery. Pharm Res 16: 1534–1541
Aubin RA, Weinfeld M, Mirzayans R, Paterson MC (1994) Polybrene/DMSO-assisted gene transfer. Generating stable transfectants with nanogram amounts of DNA. Mol Biotechnol 1:29–48
Balicki D, Putnam CD, Scaria PV, Beutler E (2002) Structure and function correlation in histone H2A peptide-mediated gene transfer. Proc Natl Acad Sci USA 99:7467–7471
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 92:7297–7301
Chan CK, Jans DA (1999) Enhancement of polylysine-mediated transferrinfection by nuclear localization sequences: polylysine does not function as a nuclear localization sequence. Hum Gene Ther 10:1695–702
Cherng JY, van de Wetering P, Talsma H, Crommelin DJ, Hennink WE (1996) Effect of size and serum proteins on transfection efficiency of poly ((2-dimethylamino)ethyl methacrylate)-plasmid nanoparticles. Pharm Res 13:1038–1042
Choi JS, Lee EJ, Choi YH, Jeong YJ, Park JS (1999a) Poly(ethylene glycol)-block-poly(Llysine) dendrimer: novel linear polymer/dendrimer block copolymer forming a spherical water-soluble polyionic complex with DNA. Bioconjug Chem 10:62–65
Choi YH, Liu F, Choi JS, Kim SW, Park JS (1999b) Characterization of a targeted gene carrier, lactose-polyethylene glycol-grafted poly-L-lysine and its complex with plasmid DNA. Hum Gene Ther 10:2657–2665
Choi YH, Liu F, Kim JS, Choi YK, Park JS, Kim SW (1998) Polyethylene glycol-grafted poly-L-lysine as polymeric gene carrier. J Control Release 54:39–48
Collins L, Fabre JW (2004) A synthetic peptide vector system for optimal gene delivery to corneal endothelium. J Gene Med 6:185–194
Cotten M, Langle-Rouault F, Kirlappos H, Wagner E, Mechtler K, Zenke M, Beug H, Birnstiel ML (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 87:4033–4037
Dash PR, Read ML, Barrett LB, Wolfert MA, Seymour LW (1999) Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery. Gene Ther 6:643–650
De Smedt SC, Demeester J, Hennink WE (2000) Cationic polymer based gene delivery systems. Pharm Res 17:113–126
Demeneix B, Behr J, Boussif O, Zanta MA, Abdallah B, Remy J (1998) Gene transfer with lipospermines and polyethylenimines. Adv Drug Deliv Rev 30:85–95
Drose S, Altendorf K (1997) Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases. J Exp Biol 200 (Pt 1):1–8
Erbacher P, Roche AC, Monsigny M, Midoux P (1995) Glycosylated polylysine/DNA complexes: gene transfer efficiency in relation with the size and the sugar substitution level of glycosylated polylysines and with the plasmid size. Bioconjug Chem 6:401–410
Erbacher P, Roche AC, Monsigny M, Midoux P (1996) Putative role of chloroquine in gene transfer into a human hepatoma cell line by DNA/lactosylated polylysine complexes. Exp Cell Res 225:186–194
Erbacher P, Roche AC, Monsigny M, Midoux P (1997) The reduction of the positive charges of polylysine by partial gluconoylation increases the transfection efficiency of polylysine/DNA complexes. Biochim Biophys Acta 1324:27–36
Erbacher P, Remy JS, Behr JP (1999) Gene transfer with synthetic virus-like particles via the integrin-mediated endocytosis pathway. Gene Ther 6:138–145
Fisher KD, Ulbrich K, Subr V, Ward CM, Mautner V, Blakey D, Seymour LW (2000) A versatile system for receptor-mediated gene delivery permits increased entry of DNA into target cells, enhanced delivery to the nucleus and elevated rates of transgene expression. Gene Ther 7:1337–1343
Fredericksen BL, Wei BL, Yao J, Luo T, Garcia JV (2002) Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus. J Virol 76: 11440–11446
Fritz JD, Herweijer H, Zhang G, Wolff JA (1996) Gene transfer into mammalian cells using histone-condensed plasmid DNA. Hum Gene Ther 7:1395–1404
Furgeson DY CW, Yockman JW, Kim SW (2003) Modified Linear Polyethylenimine-Cholesterol Comjugates for DNA Complexation. Bioconjug Chem 14:840–847
Garcia-Bustos J, Heitman J, Hall MN (1991) Nuclear protein localization. Biochim Biophys Acta 1071:83–101
Godbey WT, Wu KK, Mikos AG (1999a) Size matters: molecular weight affects the efficiency of poly(ethylenimine) as a gene delivery vehicle. J Biomed Mater Res 45:268–275
Godbey WT, Wu KK, Mikos AG (1999b) Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery. Proc Natl Acad Sci USA 96:5177–5181
Godbey WT, Barry MA, Saggau P, Wu KK, Mikos AG (2000) Poly(ethylenimine)-mediated transfection: a new paradigm for gene delivery. J Biomed Mater Res 51:321–328
Guo W, Lee RL (1999) Receptor-targeted gene delivery via folate-conjugated polyethylenimine. AAPS PharmSci 1:E19
Haensler J, Szoka Jr FC (1993) Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. Bioconjug Chem 4:372–379
Harbottle RP, Cooper RG, Hart SL, Ladhoff A, McKay T, Knight AM, Wagner E, Miller AD, Coutelle C (1998) An RGD-oligolysine peptide: a prototype construct for integrin-mediated gene delivery. Hum Gene Ther 9:1037–1047
Howard KA, Dash PR, Read ML, Ward K, Tomkins LM, Nazarova O, Ulbrich K, Seymour LW (2000) Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA. Biochim Biophys Acta 1475:245–255
Itaka (2003) 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 medicine 6:76–84
Jeong JH, Song SH, Lim DW, Lee H, Park TG (2001) DNA transfection using linear poly (ethylenimine) prepared by controlled acid hydrolysis of poly(2-ethyl-2-oxazoline). J Control Release 73:391–399
Kaiser J (2003) Gene therapy. Seeking the cause of induced leukemias in X-SCID trial. Science 299:495
Katayose S, Kataoka K (1998) Remarkable increase in nuclease resistance of plasmid DNA through supramolecular assembly with poly(ethylene glycol)-poly(L-lysine) block copolymer. J Pharm Sci 87:160–163
Kim JS, Kim BI, Maruyama A, Akaike T, Kim SW (1998) A new non-viral DNA delivery vector: the terplex system. J Control Release 53:175–182
Kimura T, Yamaoka Y, Iwase R, Murakami A (2002) Effect of physicochemical properties of polyplexes composed od chemically modified PL derivatives on transfection efficiency in vitro. Macromolecular Bioscience 2:437–446
Klink DT, Chao S, Glick MC, Scanlin TF (2001) Nuclear translocation of lactosylated poly-L-lysine/cDNA complex in cystic fibrosis airway epithelial cells. Mol Ther 3:831–841
Kopeek VuaJ, Pohl MBaVK J (1988) Cleavage of oligopeptide side-chains in N-(2-hydroxypropyl) meth-acrylamide copolymers by mixtures of lysosomal enzymes. J Control Release 8:133–140
Kunath K vHA, Fischer D, Petersen H, Bickel U, Voigt K, Kissel T (2003) Low-molecularweight polyethylenimine as a non-viral vector for DNA delivery: comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine. J Control Release 89:113–125
Kursa M, Walker GF, Roessler V, Ogris M, Roedl W, Kircheis R, Wagner E (2003) Novel shielded transferrin-polyethylene glycol-polyethylenimine/DNA complexes for systemic tumor-targeted gene transfer. Bioconjug Chem 14:222–231
Leamon CP, Weigl D, Hendren RW (1999) Folate copolymer-mediated transfection of cultured cells. Bioconjug Chem 10:947–957
Lee KY, Kwon IC, Kim YH, Jo WH, Jeong SY (1998) Preparation of chitosan self-aggregates as a gene delivery system. J Control Release 51:213–220
Lim DW, Yeom YI, Park TG (2000) Poly(DMAEMA-NVP)-β-PEG-galactose as gene delivery vector for hepatocytes. Bioconjug Chem 11:688–695
Liquier J, Pinot-Lafaix M, Taillandier E, Brahms J (1975) Infrared linear dichroism investigations of deoxyribonucleic acid complexes with poly(L-arginine) and poly(L-lysine). Biochemistry 14:4191–4197
Maes R, Sedwick W, Vaheri A (1967) Interaction between DEAE-dextran and nucleic acids. Biochim Biophys Acta 134:269–276
Magin-Lachmann C, Kotzamanis G, D’Aiuto L, Cooke H, Huxley C, Wagner E (2004) In vitro and in vivo delivery of intact BAC DNA-comparison of different methods. J Gene Med 6:195–209
Mannisto M, Vanderkerken S, Toncheva V, Elomaa M, Ruponen M, Schacht E, Urtti A (2002) Structure-activity relationships of poly(L-lysines): effects of pegylation and molecular shape on physicochemical and biological properties in gene delivery. J Control Release 83:169
Marshall E (1999) Gene therapy death prompts review of adenovirus vector. Science 286: 2244–2245
Marshall E (2000) FDA halts all gene therapy trials at Penn. Science 287:565, 567
Marshall E (2002) Clinical research. Gene therapy a suspect in leukemia-like disease. Science 298:34–35
Maxfield FR (1982) Weak bases and ionophores rapidly and reversibly raise the pH of endocytic vesicles in cultured mouse fibroblasts. J Cell Biol 95:676–681
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 21:871–878
Mislick KA, Baldeschwieler JD, Kayyem JF, Meade TJ (1995) Transfection of folatepolylysine DNA complexes: evidence for lysosomal delivery. Bioconjug Chem 6:512–515
Mita K, Zama M, Ichimura S (1977) Effect of charge density of cationic polyelectrolytes on complex formation with DNA. Biopolymers 16:1993–2004
Mumper RJ, Wang J, Klakamp SL, Nitta H, Anwer K, Tagliaferri F, Rolland AP (1998) Protective interactive noncondensing (PINC) polymers for enhanced plasmid distribution and expression in rat skeletal muscle. J Control Release 52:191–203
Murphy RF, Powers S, Cantor CR (1984) Endosome pH measured in single cells by dual fluorescence flow cytometry: rapid acidification of insulin to pH 6. J Cell Biol 98: 1757–1762
Nishikawa M, Takemura S, Takakura Y, Hashida M (1998) Targeted delivery of plasmid DNA to hepatocytes in vivo: optimization of the pharmacokinetics of plasmid DNA/galactosylated poly(L-lysine) complexes by controlling their physicochemical properties. J Pharmacol Exp Ther 287:408–415
Ogris M, Brunner S, Schuller S, Kircheis R, Wagner E (1999) PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther 6:595–605
Ohashi S, Kubo T, Ikeda T, Arai Y, Takahashi K, Hirasawa Y, Takigawa M, Satoh E, Imanishi J, Mazda O (2001) Cationic polymer-mediated genetic transduction into cultured human chondrosarcoma-derived HCS-2/8 cells. J Orthop Sci 6:75–81
Okada CY, Rechsteiner M (1982) Introduction of macromolecules into cultured mammalian cells by osmotic lysis of pinocytic vesicles. Cell 29:33–41
Plank C, Tang MX, Wolfe AR, Szoka Jr FC (1999) Branched cationic peptides for gene delivery: role of type and number of cationic residues in formation and in vitro activity of DNA polyplexes. Hum Gene Ther 10:319–332
Pollard H, Remy JS, Loussouarn G, Demolombe S, Behr JP, Escande D (1998) Polyethylenimine but not cationic lipids promotes transgene delivery to the nucleus in mammalian cells. J Biol Chem 273:7507–7511
Prasmickaite L, Hogset A, Berg K (2002) The role of the cell cycle on the efficiency of photochemical gene transfection. Biochim Biophys Acta 1570:210–218
Putnam D, Gentry CA, Pack DW, Langer R (2001) Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini. Proc Natl Acad Sci USA 98: 1200–1205
Remy-Kristensen A, Clamme JP, Vuilleumier C, Kuhry JG, Mely Y (2001) Role of endocytosis in the transfection of L929 fibroblasts by polyethylenimine/DNA complexes. Biochim Biophys Acta 1514:21–32
Ringsdorf H (1975) Structure and properties of pharmacologically active polymers. J Poly Sci Symp 51:135–153
Rosenkranz AA, Yachmenev SV, Jans DA, Serebryakova NV, Murav’ev VI, Peters R, Sobolev AS (1992) Receptor-mediated endocytosis and nuclear transport of a transfecting DNA construct. Exp Cell Res 199:323–329
Ruponen M, Yla-Herttuala S, Urtti A (1999) Interactions of polymeric and liposomal gene delivery systems with extracellular glycosaminoglycans: physicochemical and transfection studies. Biochim Biophys Acta 1415:331–341
Seymour LW (1997) Synthetic polymers for vectorial delivery of DNA: characterisation of polymer-DNA complexes by photon correlation spectroscopy and stability to nuclease degradation and disruption by polyanions in vitro. Journal of Controlled Release 48: 269–276
Seymour LW (1999) Turbidometric analysis of polyelectrolyte complexes formed between poly(L-lysine) and DNA. Colloids and Surfaces B 16:253–260
Takai T, Ohmori H (1990) DNA transfection of mouse lymphoid cells by the combination of DEAE-dextran-mediated DNA uptake and osmotic shock procedure. Biochim Biophys Acta 1048:105–109
Tang MX, Rademann CT, Szoka FC (1996) In vitro gene delivery by degraded polyamidoamine dendrimers. Bioconj Chem 6:703–714
Tang MX, Szoka FC (1997) The influence of polymer structure on the interactions of cationic polymers with DNA and morphology of the resulting complexes. Gene Ther 4:823–832
Toncheva V, Wolfert MA, Dash PR, Oupicky D, Ulbrich K, Seymour LW, Schacht EH (1998) Novel vectors for gene delivery formed by self-assembly of DNA with poly(L-lysine) grafted with hydrophilic polymers. Biochim Biophys Acta 1380:354–368
van de Wetering P, Cherng JY, Talsma H, Crommelin DJ, Hennink WE (1998) 2-(Dimethylamino) ethyl methacrylate based (co)polymers as gene transfer agents. J Control Release 53:145–153
van de Wetering P, Moret EE, Schuurmans-Nieuwenbroek NM, van Steenbergen MJ, Hennink WE (1999) Structure-activity relationships of water-soluble cationic methacrylate/methacrylamide polymers for non-viral gene delivery. Bioconjug Chem 10:589–597
Vinogradov S, Batrakova E, Li S, Kabanov A (1999) Polyion complex micelles with protein-modified corona for receptor-mediated delivery of oligonucleotides into cells. Bioconjug Chem 10:851–860
Vinogradov SV, Bronich TK, Kabanov AV (1998) Self-assembly of polyamine-poly(ethylene glycol) copolymers with phosphorothioate oligonucleotides. Bioconjug Chem 9: 805–812
Wagner E, Cotton M, Foisner R, Birnstiel ML (1991) Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells. Proc Natl Acad Sci USA 88:4255–4259
Wagner E, Cotton M, Mechtler K, Kirlappos H, Birnstiel ML (1991) DNA-binding transferring conjugates as functional gene-delivery agents: synthesis by linkage of polylysine or ethidium homodimer to the transferrin carbohydrate moiety. Bioconjug Chem 2:226–231
Wagner E, Zenke M, Cotton M, Beug H, Birnstiel ML (1990) Transferrin-polycation conjugates as carriers for DNA uptake into cells. Proc Natl Acad Sci USA 87:3410–3414
Wall DA, Wilson G, Hubbard AL (1980) The galactose-specific recognition system of mammalian liver: the route of ligand internalization in rat hepatocytes. Cell 21:79–93
Wattiaux R, Laurent N, Wattiaux-De Coninck S, Jadot M (2000) Endosomes, lysosomes: their implication in gene transfer. Adv Drug Deliv Rev 41:201–208
Wink T, Beer J, Hennink WE, Bult A, van Bennekom WP(1999) Interaction between plasmid DNA and cationic polymers studied by surface plasmon resonance spectrometry. Anal Chem 71:801–805
Wolfert MA, Dash PR, Nazarova O, Oupicky D, Seymour LW, Smart S, Strohalm J, Ulbrich K (1999) Polyelectrolyte vectors for gene delivery: influence of cationic polymer on biophysical properties of complexes formed with DNA. Bioconjug Chem 10:993–1004
Wolfert MA, Schacht EH, Toncheva V, Ulbrich K, Nazarova O, Seymour LW (1996) Characterization of vectors for gene therapy formed by self-assembly of DNA with synthetic block co-polymers. Hum Gene Ther 7:2123–2133
Wu GY, Wu CH (1987) Receptor-mediated in vitro gene transformation by a soluble DNA carrier system. J Biol Chem 262:4429–4432
Wu GY, Wu CH (1988a) Evidence for targeted gene delivery to Hep G2 hepatoma cells in vitro. Biochemistry 27:887–892
Wu GY, Wu CH (1988b) Receptor-mediated gene delivery and expression in vivo. J Biol Chem 263:14621–14624
Yamaoka T, Iwata H, Hamada N, Ide H, Kimura Y (1994) Transfection of foreign gene to mammalian cells using low-toxic cationic polymers. Nucleic Acids Symposium Series 31:229–230
Yamaoka T, Kimura T, Iwase R, Murakami A (2000) Enhanced expression of foreign gene transferred to mammalian cells in vitro using chemically modified poly(L-lysine)s as gene carriers. Chemistry Letters:118–119
Yamaoka T, Tabata Y, Ikada Y (1994) Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice. J Pharm Sci 83:601–606
Yamaoka T, Tabata Y, Ikada Y (1995) Comparison of body distribution of poly(vinyl alcohol) with other water-soluble polymers after intravenous administration. J Pharm Pharmacol 47:479–486
Yoneda Y (1997) How proteins are transported from cytoplasm to the nucleus. J Biochem (Tokyo) 121:811–817
Zanta MA, Boussif O, Adib A, Behr JP (1997) In vitro gene delivery to hepatocytes with galactosylated polyethylenimine. Bioconjug Chem 8:839–844
Zauner W, Brunner S, Buschle M, Ogris M, Wagner E (1999) 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 1428:57–67
Zenke M, Steinlein P, Wagner E, Cotton M, Beug H, Birnstiel ML (1990) Receptor-mediated endocytosis of transferrin-polycation conjugates: an efficient way to introduce DNA into hematopoietic cells. Proc Natl Acad Sci USA 87:3655–3659
Zuidam NJ, Posthuma G, de Vries ET, Crommelin DJ, Hennink WE, Storm G (2000) Effects of physicochemical characteristics of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes on cellular association and internalization. J Drug Target 8:51–66
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer-Verlag Tokyo
About this chapter
Cite this chapter
Hashimoto, T., Yamaoka, T. (2005). Polymeric Gene Carriers. In: Taira, K., Kataoka, K., Niidome, T. (eds) Non-viral Gene Therapy. Springer, Tokyo. https://doi.org/10.1007/4-431-27879-6_4
Download citation
DOI: https://doi.org/10.1007/4-431-27879-6_4
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-25122-4
Online ISBN: 978-4-431-27879-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)