Cationic Polymer Based Gene Delivery Systems

Pharmaceutical Research - Tập 17 Số 2 - Trang 113-126 - 2000
De Smedt, Stefaan C.1, Demeester, Joseph1, Hennink, Wim E.2
1Faculty of Pharmacy, Ghent University, Belgium
2Department of Pharmaceutics, University of Utrecht, the Netherlands

Tóm tắt

Gene transfer to humans requires carriers for the plasmid DNA which canefficiently and safely carrythe gene into the nucleus of the desired cells. A series of chemically differentcationic polymers arecurrently being investigated for these purposes. Although many cationic polymersindeed condense DNAspontaneously, which is a requirement for gene transfer in most types of cells,the physicochemical andbiopharmaceutical behavior of the current generation of polyplexes severelylimits an efficient genetransfer in vitro and especially in vivo. This papersummarizes recent physicochemical and biologicalinformation on polyplexes and aims to provide new insights with respect to thistype of gene deliverysystem. Firstly, the chemical structure of frequently studied cationic polymersis represented. Secondly,the parameters influencing condensation of DNA by cationic polymers aredescribed. Thirdly, the surfaceproperties, solubility, aggregration behavior, degradation and dissociation ofpolyplexes are considered.The review ends by describing the in vitro and in vivo genetransfection behavior of polyplexes.

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citation_journal_title=J. Contr. Rel.; citation_title=Protective interactive noncon-densing (PINC) polymers for enhanced plasmid distribution and expression in rat skeletal muscle; citation_author=R. J. Mumper, J. J. Wang, S. L. Klakamp, H. Nitta, K. Anwer, F. Tagliaferri, A. P. Rolland; citation_volume=52; citation_publication_date=1998; citation_pages=191-203; citation_id=CR1

citation_journal_title=Bioconjug. Chem.; citation_title=Nanoparticle DNAcarrier with poly(L-lysine) grafted polysaccharide copolymer and poly(D,L-lactic acid); citation_author=A. Maruyama, T. Ishihara, J. S. Kim, S. W. Kim, T. Akaike; citation_volume=8; citation_publication_date=1997; citation_pages=735-742; citation_id=CR2

citation_journal_title=Hum. Gene Ther.; citation_title=Nomenclature for synthetic gene delivery systems; citation_author=P. L. Felgner, Y. Barenholz, J. P. Behr, S. H. Cheng, P. Cullis, L. Huang, J. A. Jessee, L. Seymour, F. Szoka, A. R. Thierry, E. Wagner, G. Wu; citation_volume=8; citation_publication_date=1997; citation_pages=511-512; citation_id=CR3

citation_journal_title=Hum. Gene Ther.; citation_title=Pulmonary surfactant inhibits cationic liposome-mediated gene delivery to respiratory epithelial cells in vitro; citation_author=J. E. Duncan, J. A. Whitsett, A. D. Horowitz; citation_volume=8; citation_publication_date=1997; citation_pages=431-438; citation_id=CR4

N. Ernst, S. Ulrichskötter, W. A. Schmalix, J. Rädler, R. Galneder, E. Mayer, S. Gersting, C. Plank, D. Reinhardt, and J. Rosenacker. Interaction of liposomal and polycationic transfection complexes with pulmonray surfactant. J. Gen. Med. Preprint 1: in press (1999).

citation_journal_title=Sci. Am.; citation_title=Non viral strategies for gene therapy; citation_author=P. L. Felgner; citation_volume=276; citation_publication_date=1997; citation_pages=102-106; citation_id=CR6

citation_journal_title=J. Contr. Rel.; citation_title=Controllable gene therapy- pharmaceutics of non-viral gene delivery systems; citation_author=E. Tomlinson, A. P. Rolland; citation_volume=39; citation_publication_date=1996; citation_pages=357-372; citation_id=CR7

citation_journal_title=Pharm. Res.; citation_title=Pharmaceutical approach to somatic gene therapy; citation_author=F. D. Ledley; citation_volume=13; citation_publication_date=1996; citation_pages=1595-1614; citation_id=CR8

citation_journal_title=Adv. Drug Deliv. Rev.; citation_title=Gene transfer with lipospermines and polyethylene-imines; citation_author=J. S. Remy, B. Abdallah, M. A. Zanta, O. Boussif, J. P. Behr, B. Demeneix; citation_volume=30; citation_publication_date=1998; citation_pages=85-95; citation_id=CR9

citation_journal_title=Adv. Drug Del. Rev.; citation_title=Polylysine-based transfection systems utilizing receptor-mediated delivery; citation_author=W. Zauner, M. Ogris, E. Wagner; citation_volume=30; citation_publication_date=1998; citation_pages=97-113; citation_id=CR10

citation_journal_title=Biochim. Biophys. Acta; citation_title=DNA transfection of mouse lymphoid-cells by the combination of DEAE-dextran-mediated DNA uptake and osmotic shock procedure; citation_author=T. Takai, H. Ohmori; citation_volume=1048; citation_publication_date=1990; citation_pages=105-109; citation_id=CR11

G. Y. Wu and C. H. Wu. Receptor-mediated in vitro gene transformation by a soluble DNA carrier system. J. Biol. Chem. 4429-4432 (1987).

citation_journal_title=Adv. Drug Del. Rev.; citation_title=Synthetic peptide-based DNA complexes for nonviral gene delivery; citation_author=L. C. Smith, J. Duguid, M. S. Wadhwa, M. J. Logan, C. H. Tung, V. Edwards, J. T. Sparrow; citation_volume=30; citation_publication_date=1998; citation_pages=115-131; citation_id=CR13

citation_journal_title=Biophys. J.; citation_title=A physicochemical approach for predicting the effectiveness of peptide-based gene delivery systems for use in plasmid-based gene therapy; citation_author=J. G. Duguid, C. Li, M. Shi, M. J. Logan, H. Alila, A. Rolland, E. Tomlinson, J. T. Sparrow, L. C. Smith; citation_volume=74; citation_publication_date=1998; citation_pages=2802-2814; citation_id=CR14

citation_journal_title=Adv. Drug Del. Rev.; citation_title=Interpolyelectrolyte and block ionomer complexes for gene delivery: physicochemical aspects; citation_author=A. V. Kabanov, V. A. Kabanov; citation_volume=30; citation_publication_date=1998; citation_pages=49-60; citation_id=CR15

citation_journal_title=Hum. Gene Ther.; citation_title=Characterization of vectors for gene therapy formed by self-assembly of DNA with synthetic block co-polymers; citation_author=M. A. Wolfert, E. H. Schacht, V. Toncheva, K. Ulbrich, O. Nazarova, L. W. Seymour; citation_volume=7; citation_publication_date=1996; citation_pages=2123-2133; citation_id=CR16

citation_journal_title=Biochim. Biophys. Acta Gen. Rev.; citation_title=Novel Vectors for gene delivery formed by self-assembly of DNA with poly(L-lysine) grafted with hydrophilic polymers; citation_author=V. Toncheva, M. A. Wolfert, P. R. Dash, D. Oupicky, K. Ulbrich, L. W. Seymour, E. H. Schacht; citation_volume=1380; citation_publication_date=1998; citation_pages=354-368; citation_id=CR17

citation_journal_title=Bioconjug. Chem.; citation_title=Comb-type polycations effectively stabilize DNA triplex; citation_author=A. Maruyama, M. Katoh, T. Ishihara, T. Akaike; citation_volume=8; citation_publication_date=1997; citation_pages=3-6; citation_id=CR18

citation_journal_title=Bioconjug. Chem.; citation_title=Characterization of interpolyelectrolyte complexes between double-stranded DNA and polylysine comb-type copolymers having hydrophilic side chains; citation_author=A. Maruyama, H. Watanabe, A. Ferdous, M. Katoh, T. Ishihara, T. Akaike; citation_volume=9; citation_publication_date=1998; citation_pages=292-299; citation_id=CR19

citation_journal_title=Bioconjug. Chem.; citation_title=Water-soluble polyion complex associates of DNA and poly(ethylene glycol) poly(L-lysine) block copolymer; citation_author=S. Katayose, K. Kataoka; citation_volume=8; citation_publication_date=1997; citation_pages=702-707; citation_id=CR20

citation_journal_title=J. Pharm. Sci.; citation_title=Remarkable increase in nuclease resistance of plasmid DNA through supramolecular assembly with poly(ethylene glycol) poly(L-lysine) block copolymer; citation_author=S. Katayose, K. Kataoka; citation_volume=87; citation_publication_date=1998; citation_pages=160-163; citation_id=CR21

J. Haensler and F. C. J. Szoka. Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. Bioconjug. Chem. 372-379 (1993).

citation_journal_title=Gene Ther.; citation_title=Optimized galenics improve in vitro gene transfer with cationic molecules up to 1000-fold; citation_author=O. Boussif, M. A. Zanta, J. P. Behr; citation_volume=3; citation_publication_date=1996; citation_pages=1074-1080; citation_id=CR23

citation_journal_title=Bioconjug. Chem.; citation_title=In vitro gene delivery to hepatocytes with galactosylated polyethylenimine; citation_author=M. A. Zanta, O. Boussif, A. Adib, J. P. Behr; citation_volume=8; citation_publication_date=1997; citation_pages=839-844; citation_id=CR24

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine; citation_author=O. Boussif, F. Lezoualc'h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, J. P. Behr; citation_volume=92; citation_publication_date=1995; citation_pages=7297-7301; citation_id=CR25

citation_journal_title=Gene Ther.; citation_title=ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo; citation_author=S. Ferrari, E. Moro, A. Pettenazzo, J. P. Behr, F. Zacchello, M. Scarpa; citation_volume=4; citation_publication_date=1997; citation_pages=1100-1106; citation_id=CR26

citation_journal_title=Pharm. Res.; citation_title=Effect of size and serum proteins on transfection efficiency of poly((2-dimethylamino)ethyl methacrylate)-plasmid nanoparticles; citation_author=J.-Y. Cherng, P. v. d. Wetering, H. Talsma, D. J. A. Crommelin, W. E. Hennink; citation_volume=13; citation_publication_date=1996; citation_pages=1038-1042; citation_id=CR27

citation_journal_title=J. Cont. Rel.; citation_title=Relation between transfection efficiency and cytotoxicity of poly(2-(dimethylamino)ethyl mathacrylate)/plasmid complexes; citation_author=P. v. d. Wetering, J.-Y. Cherng, H. Talsma, W. E. Hennink; citation_volume=49; citation_publication_date=1997; citation_pages=59-69; citation_id=CR28

citation_journal_title=J. Contr. Rel.; citation_title=Chitosan and depolymerized chitosan oligomers as condensing carriers for in vivo plasmid delivery; citation_author=F. C. MacLaughlin, R. J. Mumper, J. Wang, F. Tagliaferri, I. Gill, M. Hinchcliffe, A. Rolland; citation_volume=56; citation_publication_date=1998; citation_pages=259-272; citation_id=CR29

citation_journal_title=Biochemistry; citation_title=Evidence for targeted gene delivery to Hep G2 hepatoma cells in vitro; citation_author=G. Y. Wu, C. H. Wu; citation_volume=27; citation_publication_date=1988; citation_pages=887-892; citation_id=CR30

citation_journal_title=Bioconjug.; citation_title=DNA complexes with polycations for the delivery of genetic material into cells; citation_author=A. V. Kabanov, V. A. Kabanov; citation_volume=6; citation_publication_date=1995; citation_pages=7-20; citation_id=CR31

citation_title=Ligand-polylysine mediated gene transfer; citation_inbook_title= ; citation_publication_date=1996; citation_pages=120-128; citation_id=CR32; citation_author=A. Kichler; citation_author=W. Zauner; citation_author=C. Morrison; citation_author=E. Wagner; citation_publisher=ACS

citation_journal_title=Biopolymers; citation_title=Condensation of DNA by multivalent cations: considerations on mechanism; citation_author=V. A. Bloomfield; citation_volume=31; citation_publication_date=1991; citation_pages=1471-1481; citation_id=CR33

citation_journal_title=Curr. Opin. Struc. Biol.; citation_title=DNA condensation; citation_author=V. A. Bloomfield; citation_volume=6; citation_publication_date=1996; citation_pages=334-341; citation_id=CR34

citation_journal_title=J. Contr. Rel.; citation_title=Polycation-DNA complexes for gene delivery: a comparison of the biopharmaceutical properties of cationic polypeptides and cationic lipids; citation_author=C. W. Pouton, P. Lucas, B. J. Thomas, A. N. Uduehi, D. A. Milroy, S. H. Moss; citation_volume=53; citation_publication_date=1998; citation_pages=289-299; citation_id=CR35

citation_journal_title=Biophys. J.; citation_title=Topological defects and the optimum size of DNA condensates; citation_author=S. Y. Park, D. Harries, W. M. Gelbart; citation_volume=75; citation_publication_date=1998; citation_pages=714-720; citation_id=CR36

citation_journal_title=Gene Therapy; citation_title=The influence of polymer structure on the interactions of cationic polymers with DNA and morphology of the resulting complexes; citation_author=M. X. Tang, F. C. Szoka; citation_volume=4; citation_publication_date=1997; citation_pages=823-832; citation_id=CR37

citation_journal_title=Gene Ther.; citation_title=Atomic force microscopic analysis of the influence of the molecular weight of poly(L)lysine on the size of polyelectrolyte complexes formed with DNA.; citation_author=M. A. Wolfert, L. W. Seymour; citation_volume=3; citation_publication_date=1996; citation_pages=269-273; citation_id=CR38

citation_journal_title=Biochim. Biophys. Acta; citation_title=The interaction of plasmid DNA with polyamidoamine dendrimers: mechanism of complex formation and analysis of alterations induced in nuclease sensitivity and transcriptional activity of the complexed DNA; citation_author=A. U. Bielinska, J. F. KukowskaLatallo, J. R. Baker; citation_volume=1353; citation_publication_date=1997; citation_pages=180-190; citation_id=CR39

citation_journal_title=J. Biol. Chem.; citation_title=DNA aggregation induced by polyamines and cobalthexamine; citation_author=J. Pelta, F. Livolant, J. L. Sikorav; citation_volume=271; citation_publication_date=1996; citation_pages=5656-5662; citation_id=CR40

citation_journal_title=Pharm. Res.; citation_title=Terplex DNA delivery system as a gene carrier; citation_author=J. S. Kim, A. Maruyama, T. Akaike, S. W. Kim; citation_volume=15; citation_publication_date=1998; citation_pages=116-121; citation_id=CR41

J.-Y. Cherng, N. M. E. Schuurmans-Nieuwenbroek, W. Jiskoot, H. Talsma, N. J. Zuidam, W. E. Hennink, and D. J. A. Crommelin. Effect of DNA topology on the transfection efficiency of poly((2-dimethylamino)ethyl methacrylate)-plasmid complexes. J. Contr. Rel. (1999, in press).

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Transferrin-4: polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells; citation_author=E. Wagner, M. Cotten, R. Foisner, M. L. Birnstiel; citation_volume=88; citation_publication_date=1991; citation_pages=4255-4259; citation_id=CR43

citation_journal_title=J. Pharm. Sci.; citation_title=Stability of peptide condensed plasmid DNA formulations; citation_author=R. C. Adami, W. T. Collard, S. A. Gupta, K. Y. Kwok, J. Bonadio, K. G. Rice; citation_volume=87; citation_publication_date=1998; citation_pages=678-683; citation_id=CR44

citation_journal_title=Proc. Intern. Symp. Control. Rel. Bioact. Mater.; citation_title=Novel polymeric condensing carriers for gene delivery; citation_author=R. J. Mumper, J. Wang, J. M. Claspell, A.P. Rolland; citation_volume=22; citation_publication_date=1995; citation_pages=178-179; citation_id=CR45

citation_journal_title=Biopolymers; citation_title=Condensation of DNA by trivalent cations. 1. Effects of DNA length and topology on the size and shape of condensed particles; citation_author=P. G. Arscott, V. A. Bloomfield; citation_volume=30; citation_publication_date=1990; citation_pages=619-630; citation_id=CR46

citation_journal_title=J. Contr. Rel.; citation_title=In vitro gene expression on smooth muscle cells using a terplex delivery system; citation_author=J. S. Kim, A. Maruyama, T. Akaike, S. W. Kim; citation_volume=47; citation_publication_date=1997; citation_pages=51-59; citation_id=CR47

citation_journal_title=J Biol. Chem.; citation_title=Biochemical and functional characterization of DNA complexes capable of targeting genes to hepatocytes via the asialoglycoprotein receptor; citation_author=J. C. Perales, G. A. Grossmann, M. Molas, G. Liu, T. Ferkol, J. Harpst, H. Oda, R. W. Hanson; citation_volume=272; citation_publication_date=1997; citation_pages=7398-7407; citation_id=CR48

citation_journal_title=Hum. Gene Ther.; citation_title=Activation of the complement system by synthetic DNA complexes: A potential barrier for intravenous gene delivery; citation_author=C. Plank, K. Mechtler, F. C. Szoka, E. Wagner; citation_volume=7; citation_publication_date=1996; citation_pages=1437-1446; citation_id=CR49

citation_journal_title=Hum. Gene Ther.; citation_title=Gene transfer by DNA/glycosylated polylysine complexes into human blood monocyte-derived macrophages; citation_author=P. Erbacher, M. T. Bousser, J. Raimond, M. Monsigny, P. Midoux, A. C. Roche; citation_volume=7; citation_publication_date=1996; citation_pages=721-729; citation_id=CR50

citation_journal_title=Biochim. Biophys. Acta Biomembr.; citation_title=The reduction of the positive charges of polylysine by partial gluconoylation increases the transfection efficiency of polylysine/DNA complexes; citation_author=P. Erbacher, A. C. Roche, M. Monsigny, P. Midoux; citation_volume=1324; citation_publication_date=1997; citation_pages=27-36; citation_id=CR51

citation_journal_title=Macromol. Rapid Comm.; citation_title=Conjugates of polylysine and oligo(N,N-diethylacrylamide) as temperature-sensitive agents in DNA condensation; citation_author=L. Bromberg, G. Levin; citation_volume=19; citation_publication_date=1998; citation_pages=79-82; citation_id=CR52

citation_journal_title=Bioconjug. Chem.; citation_title=Design of comb-type polyamine copolymers for a novel pH-sensitive DNA carrier; citation_author=S. Asayama, A. Maruyama, C. S. Cho, T. Akaike; citation_volume=8; citation_publication_date=1997; citation_pages=833-838; citation_id=CR53

citation_journal_title=Macromolecules; citation_title=Amechanistic study of the hydrolytic stability of poly(2-(dimethy-lamino)ethyl methacrylate); citation_author=P. van de Wetering, N. J. Zuidam, M. J. v. Steenbergen, O. A. G. J. v. d. Houwen, W. J. M. Underberg, W. E. Hennink; citation_volume=31; citation_publication_date=1998; citation_pages=8063-8068; citation_id=CR54

citation_journal_title=Biopolymers; citation_title=Interaction of DNA with heavy metal ions and polybases; citation_author=I. R. Miller, D. Bach; citation_volume=6; citation_publication_date=1968; citation_pages=169-179; citation_id=CR55

citation_journal_title=Biochem. Biophys. Acta; citation_title=Interactions of polymeric and liposomal gene delivery systems with extracellular glycosaminoglycans: physicochemical and transfection studies; citation_author=M. Ruponen, S. Yla-Herttuala, A. Urtti; citation_volume=1415; citation_publication_date=1999; citation_pages=331-341; citation_id=CR56

citation_journal_title=Macromol. Symp.; citation_title=Competitive reactions in solutions of DNA-containing polyelectrolyte complexes; citation_author=V. A. Izumrudov, M. V. Zhiryakova, S. I. Kargov, A. B. Zezin, V. A. Kabanov; citation_volume=106; citation_publication_date=1996; citation_pages=179-192; citation_id=CR57

citation_journal_title=J. Contr. Rel.; citation_title=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; citation_author=P. R. Dash, V. Toncheva, E. Schacht, L. W. Seymour; citation_volume=48; citation_publication_date=1997; citation_pages=269-276; citation_id=CR58

citation_journal_title=Anal. Chem.; citation_title=Interaction between plasmid DNA and cationic polymers studied with surface plasmon resonance spectrometry; citation_author=T. Wink, J. d. Beer, P. J. H. J. v. Oss, W. N. E. van Dijk-Wolthuis, N. J. Zuidam, W. E. Hennink, A. Bult, W. P. van Bennekom; citation_volume=71; citation_publication_date=1999; citation_pages=801-805; citation_id=CR59

citation_journal_title=Gene Ther.; citation_title=Direct gene transfer to mouse melanoma by intratumor injection of free DNA; citation_author=J. P. Yang, L. Huang; citation_volume=3; citation_publication_date=1996; citation_pages=542-548; citation_id=CR60

citation_journal_title=Gene Ther.; citation_title=The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells; citation_author=M. Ogris, P. Steinlein, M. Kursa, K. Mechtler, R. Kircheis, E. Wagner; citation_volume=5; citation_publication_date=1998; citation_pages=1425-1433; citation_id=CR61

citation_journal_title=Cell; citation_title=High efficiency transformation by direct microinjection of DNA into cultured mammalian cells; citation_author=M. R. Capecchi; citation_volume=22; citation_publication_date=1980; citation_pages=479-488; citation_id=CR62

citation_title=Manipulating the trafficking of nucleic acids; citation_inbook_title= ; citation_publication_date=1997; citation_pages=135-180; citation_id=CR63; citation_author=B. Meyer; citation_author=L. S. Uyechi; citation_author=F. C. J. Szoka; citation_publisher=Marcel Dekker

citation_journal_title=Gene Ther.; citation_title=Efficacy of a peptide-based gene delivery system depends on mitotic activity; citation_author=M. Wilke, E. Fortunati, M. v. d. broek, A. T. Hoogeveen, B. J. Scholte; citation_volume=3; citation_publication_date=1996; citation_pages=1133-1142; citation_id=CR64

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Hindered diffusion of inert tracer particles in the cytoplasm of mouse 3T3 cells; citation_author=K. L. Phelps, P. E. Castle, D. L. Taylor, F. Lanni; citation_volume=84; citation_publication_date=1987; citation_pages=4910-4913; citation_id=CR65

citation_journal_title=Nature; citation_title=Nucleocytoplasmic transport: signals, mechanisms and regulation; citation_author=E. A. Nigg; citation_volume=386; citation_publication_date=1997; citation_pages=779-787; citation_id=CR66

citation_journal_title=Bioconjug. Chem.; citation_title=In vitro gene delivery by degraded polyamidoamine dendrimers; citation_author=M. X. Tang, C. T. Redemann, F. C. Szoka; citation_volume=7; citation_publication_date=1996; citation_pages=703-714; citation_id=CR67

citation_journal_title=Me´dicine/Sciences; citation_title=L' éponge àprotons: un moyen d'entrer dans une cellule auquel les virus n'ont pas pense´; citation_author=J. P. Behr; citation_volume=12; citation_publication_date=1996; citation_pages=56-59; citation_id=CR68

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Evidence for the role of proteoglycans in cation-mediated gene transfer; citation_author=K. A. Mislick, J. D. Baldeschwieler; citation_volume=93; citation_publication_date=1996; citation_pages=12349-12354; citation_id=CR69

citation_journal_title=FEBS lett.; citation_title=DNA affinity to biological membranes is enhanced due to complexation with hydrophobized polycation; citation_author=A. A. Yaroslavov, S. A. Sukhishvili, O. L. Obolsky, E. G. Yaroslavova, A. V. Kabanov, V. A. Kabanov; citation_volume=384; citation_publication_date=1996; citation_pages=177-180; citation_id=CR70

citation_journal_title=J. Contr. Rel.; citation_title=2-(Dimethylamino)ethyl methacrylate based (co)polymers as gene transfer agents; citation_author=P. van de Wetering, J.-Y. Cherng, H. Talsma, D. J. A. Crommelin, W. E. Hennink; citation_volume=53; citation_publication_date=1998; citation_pages=145-153; citation_id=CR71

citation_journal_title=J. Contr. Rel.; citation_title=Polyethylene glycol-grafted poly-L-lysine as polymeric gene carrier; citation_author=Y. H. Choi, F. Liu, J. S. Kim, Y. K. Choi, J. S. Park, S. W. Kim; citation_volume=54; citation_publication_date=1998; citation_pages=39-48; citation_id=CR72

citation_journal_title=Biochemistry; citation_title=Deformation and instability in membrane structure of phospholipid vesicles caused by osmophobic association: mechanical stress model for the mechanism of poly(ethylene glycol)-induced membrane fusion; citation_author=M. Yamazaki, T. Ito; citation_volume=29; citation_publication_date=1990; citation_pages=1309-1314; citation_id=CR73

citation_journal_title=Trends Pharmacol. Sci.; citation_title=Structure and morphology of the proton-ATPases; citation_author=N. Nelson; citation_volume=12; citation_publication_date=1991; citation_pages=71-75; citation_id=CR74

citation_journal_title=Methods Enzymol.; citation_title=Inhibitors of lysosomal function; citation_author=P. O. Seglen; citation_volume=96; citation_publication_date=1983; citation_pages=737-764; citation_id=CR75

citation_journal_title=Exp. Cell Res.; citation_title=Putative role of chloroquine in gene transfer into a human hepatoma cell line by DNA lactosylated polylysine complexes; citation_author=P. Erbacher, A. C. Roche, M. Monsigny, P. Midoux; citation_volume=225; citation_publication_date=1996; citation_pages=186-194; citation_id=CR76

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Adenovirus enhancement of transferrin polylysine-mediated gene delivery; citation_author=D. T. Curiel, S. Agarwal, E. Wagner, M. Cotten; citation_volume=88; citation_publication_date=1991; citation_pages=8850-8854; citation_id=CR77

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=High-efficiency receptor-mediated delivery of small and large (48 kilobase) gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles; citation_author=M. Cotten, E. Wagner, K. Zatloukal, S. Phillips, D. T. Curiel, M. L. Birnstiel; citation_volume=89; citation_publication_date=1992; citation_pages=6094-6098; citation_id=CR78

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Coupling of adenovirus to transferrin polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes; citation_author=E. Wagner, K. Zatloukal, M. Cotten, H. Kirlappos, K. Mechtler, D. T. Curiel, M. L. Birnstiel; citation_volume=89; citation_publication_date=1992; citation_pages=6099-6103; citation_id=CR79

citation_journal_title=J. Biol. Chem.; citation_title=Membrane binding and conformational properties of peptides representing the NH2 terminus of influenza HA2; citation_author=J. D. Lear, W. F. DeGrado; citation_volume=262; citation_publication_date=1987; citation_pages=6500-6505; citation_id=CR80

citation_journal_title=J. Biol. Chem.; citation_title=The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems; citation_author=C. Plank, B. Oberhauser, K. Mechtler, C. Koch, E. Wagner; citation_volume=269; citation_publication_date=1994; citation_pages=12918-12924; citation_id=CR81

citation_journal_title=J. Virol.; citation_title=Rhinovirus-mediated endosomal release of transfection complexes; citation_author=W. Zauner, D. Blaas, E. Kuechler, E. Wagner; citation_volume=69; citation_publication_date=1995; citation_pages=1085-1092; citation_id=CR82

citation_journal_title=J. Invest. Med.; citation_title=Design of polymers to increase the efficiency of endosomal release of drugs; citation_author=A. F. Santos, N. Murthy, P. S. Stayton, O. W. Press, D. A. Tirell, A. S. Hoffman; citation_volume=46; citation_publication_date=1998; citation_pages=91A-91A; citation_id=CR83

citation_journal_title=Biochim. Biophys. Acta Biomembr.; citation_title=Kinetics of membrane micellization by the hydrophobic polyelectrolyte poly(2-ethyla-intracellular crylic acid); citation_author=J. L. Thomas, B. P. Devlin, D. A. Tirrell; citation_volume=1278; citation_publication_date=1996; citation_pages=73-78; citation_id=CR84

citation_journal_title=Nucleic Acids Res.; citation_title=Phosphorothioate oligodeoxyribonucleotides dissociate from cationic lipids before entering the nucleus; citation_author=E. G. Marcusson, B. Bhat, M. Manoharan, C. F. Bennett, N. M. Dean; citation_volume=2; citation_publication_date=1998; citation_pages=2016-2023; citation_id=CR85

citation_journal_title=Hum. Gene Ther.; citation_title=Phase I study to the immunotherapy of metastatic malignant melanoma by a cancer vaccine consisting of autologous cancer cells transfected with the human IL-2 gene; citation_author=G. Stingl, E. B. Brocker, R. Mertelsmann, K. Wolff, S. Schreiber, E. Kampgen, A. Schneeberger, W. Dummer, U. Brennscheid, H. Veelken, M. L. Birnstiel, K. Zatloukal, W. Schmidt, G. Maass, E. Wagner, M. Buschle, M. Giese, E. R. Kempe, H. A. Weber, T. Voigt; citation_volume=7; citation_publication_date=1996; citation_pages=551-563; citation_id=CR86

citation_journal_title=J. Gen. Med. Preprint; citation_title=Polycation-based DNA complexes for tumor-targeted gene delivery in vivo ; citation_author=R. Kircheis, S. Schüller, S. Brunner, M. Ogris, K.-H. Heider, W. Zauner, E. Wagner; citation_volume=d1; citation_publication_date=1999; citation_pages=1-16; citation_id=CR87

citation_journal_title=J. Biol. Chem.; citation_title=Receptor-mediated gene delivery and expression in vivo; citation_author=G. Y. Wu, C. H. Wu; citation_volume=263; citation_publication_date=1988; citation_pages=14621-14624; citation_id=CR88

citation_journal_title=J. Biol. Chem.; citation_title=Fate of DNA targeted to the liver by asialoglycoprotein receptor-mediated endocytosis in vivo ; citation_author=N. R. Chowdhury, C. H. Wu, G. Y. Wu, V. R. Yerneni, V. R. Bommineni, J. R. Chowdhury; citation_volume=68; citation_publication_date=1993; citation_pages=2341-2346; citation_id=CR89

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Gene transfer in vivo: sustained expression and regulation of genes introduced into the liver by receptor-targeted uptake; citation_author=J. C. Perales, T. Ferkol, H. Beegen, O. D. Ratnoff, R. W. Hanson; citation_volume=91; citation_publication_date=1994; citation_pages=4086-4090; citation_id=CR90

citation_journal_title=J. Contr. Rel.; citation_title=Targeted delivery of plasmid DNA complexed with galactosylated poly(L-Lysine); citation_author=M. Hashida, S. Takemura, M. Nishikawa, Y. Takakura; citation_volume=53; citation_publication_date=1998; citation_pages=301-310; citation_id=CR91

citation_journal_title=J. Clin. Invest.; citation_title=Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor; citation_author=T. Ferkol, J. C. Perales, E. Eckman, C. S. Kaetzel, R. W. Hanson, P. B. Davis; citation_volume=95; citation_publication_date=1995; citation_pages=493-502; citation_id=CR92

citation_journal_title=Gene Ther.; citation_title=Gene transfer by naked DNA into adult mouse brain; citation_author=B. Schwartz, C. Benoist, B. Abdallah, R. Rangara, A. Hassan, D. Scherman, B. A. Demeneix; citation_volume=3; citation_publication_date=1996; citation_pages=405-411; citation_id=CR93

citation_journal_title=Hum. Gene Ther.; citation_title=Nonviral gene delivery to the rat kidney with polyethy-lenimine; citation_author=A. Boletta, A. Benigni, J. Lutz, G. Remuzzi, M. R. Soria, L. Monaco; citation_volume=8; citation_publication_date=1997; citation_pages=1243-1251; citation_id=CR94

citation_journal_title=Hum. Gene Ther.; citation_title=Efficient transfer of genes into murine cardiac grafts by starburst polyamidoamine dendrimers; citation_author=L. H. Qin, D. R. Pahud, Y. Z. Ding, A. U. Bielinska, J. F. KukowskaLatallo, J. R. Baker, J. S. Bromberg; citation_volume=9; citation_publication_date=1998; citation_pages=553-560; citation_id=CR95

citation_journal_title=Bioconjug. Chem.; citation_title=Synthesis of novel polyampholyte comb-type copolymers consisting of a poly(L-lysine) backbone and hyaluronic acid side chains for a DNA carrier; citation_author=S. Asayama, M. Nogawa, Y. Takei, T. Akaike, A. Maruyama; citation_volume=9; citation_publication_date=1998; citation_pages=476-481; citation_id=CR96

citation_journal_title=J. Biol. Chem.; citation_title=Targeting genes: delivery and persistent expression of a foreign gene driven by mammalian regulatory elements in vivo; citation_author=C. H. Wu, J. M. Wilson, G. Y. Wu; citation_volume=264; citation_publication_date=1989; citation_pages=16985-16987; citation_id=CR97

citation_journal_title=Nucleic Acids Res.; citation_title=Enhanced resistance to nuclease degradation of nucleic acids complexed to asialoglycoprotein-polylysine carriers; citation_author=H. C. Chiou, M. V. Tangco, S. M. Levine, D. Robertson, K. Kormis, C. H. Wu, G. Y. Wu; citation_volume=22; citation_publication_date=1994; citation_pages=5439-5446; citation_id=CR98

citation_journal_title=Bioconjug. Chem.; citation_title=Gene transfer into hepatocytes using asialoglycoprotein receptor mediated endocytosis of DNA complexed with an artificial tetra-antennary galactose ligand; citation_author=C. Plank, K. Zatloukal, M. Cotten, K. Mechtler, E. Wagner; citation_volume=3; citation_publication_date=1992; citation_pages=533-539; citation_id=CR99

citation_journal_title=Nucleic Acids Res.; citation_title=Specific gene transfer mediated by lactosylated poly-L-lysine into hepatoma cells; citation_author=P. Midoux, C. Mendes, A. Legrand, J. Raimond, R. Mayer, M. Monsigny, A. C. Roche; citation_volume=21; citation_publication_date=1993; citation_pages=871-878; citation_id=CR100

citation_journal_title=Exp. Cell. Res.; citation_title=Receptor-mediated endocytosis and nuclear transport of a transfecting DNA construct; citation_author=A. A. Rosenkranz, S. V. Yachmenev, D. A. Jans, N. V. Serebryakova, V. I. Murav'ev, R. Peters, A. S. Sobolev; citation_volume=199; citation_publication_date=1992; citation_pages=323-329; citation_id=CR101

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Receptor mediated gene transfer into macrophages; citation_author=T. Ferkol, J. C. Perales, F. Mularo, R. W. Hanson; citation_volume=93; citation_publication_date=1996; citation_pages=101-105; citation_id=CR102

citation_journal_title=J. Clin. Invest.; citation_title=Gene transfer into respiratory epithelial cells by targeting the polymeric immunoglo-buline receptor; citation_author=T. Ferkol, C. S. Kaetzel, P. B. Davis; citation_volume=92; citation_publication_date=1993; citation_pages=2394; citation_id=CR103

citation_journal_title=Bioconjug. Chem.; citation_title=Use of N-terminal modified poly(L-lysine)-antibody conjugate as a carrier for targeted gene delivery in mouse lung endothelial cells; citation_author=V. S. Trubetskoy, V. P. Torchilin, S. J. Kennel, L. Huang; citation_volume=3; citation_publication_date=1992; citation_pages=323-327; citation_id=CR104

citation_journal_title=FEBS Lett.; citation_title=A novel gene delivery system using EGF receptor-mediated endocytosis; citation_author=J. B. Chen, S. Gamou, A. Takayanagi, N. Shimizu; citation_volume=338; citation_publication_date=1994; citation_pages=167-169; citation_id=CR105

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Transferrin-polycation conjugates as carriers for DNA uptake into cells; citation_author=E. Wagner, M. Zenke, M. Cotten, H. Beug, M. L. Birnstiel; citation_volume=87; citation_publication_date=1990; citation_pages=3410-3414; citation_id=CR106

citation_journal_title=Proc. Natl. Acad. Sci. USA; citation_title=Influenza-virus hemagglutinin-HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes: toward a synthetic virus-like genetransfer vehicle; citation_author=E. Wagner, C. Plank, K. Zatloukal, M. Cotten, M. L. Birnstiel; citation_volume=89; citation_publication_date=1992; citation_pages=7934-7938; citation_id=CR107

citation_journal_title=Bioconjug. Chem.; citation_title=Targeted gene delivery with a low molecular weight glycopeptide carrier; citation_author=M. S. Wadhwa, D. L. Knoell, A. P. Young, K. G. Rice; citation_volume=6; citation_publication_date=1995; citation_pages=283-291; citation_id=CR108

citation_journal_title=Carbohyd. Polym.; citation_title=Possibility of application of quaternary chitosan having pendant galactose residues as gene delivery tool; citation_author=J. Murata, Y. Ohya, T. Ouchi; citation_volume=29; citation_publication_date=1996; citation_pages=69-74; citation_id=CR109

citation_journal_title=Annu. Rev. Biochem.; citation_title=Hormonal regulation of mammalian glucose transport; citation_author=I. A. Simpson, S. W. Cushman; citation_volume=55; citation_publication_date=1986; citation_pages=1059-1089; citation_id=CR110