Cationic polymer based gene delivery systems

被引:763
作者
De Smedt, SC [1 ]
Demeester, J
Hennink, WE
机构
[1] State Univ Ghent, Fac Pharm, B-9000 Ghent, Belgium
[2] Univ Utrecht, Dept Pharmaceut, NL-3508 TC Utrecht, Netherlands
关键词
cationic polymers; polycations; DNA plasmid; non-viral gene therapy; gene carriers;
D O I
10.1023/A:1007548826495
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Gene transfer to humans requires carriers for the plasmid DNA which can efficiently and safely carry the gene into the nucleus of the desired cells. A series of chemically different cationic polymers are currently being investigated for these purposes. Although many cationic polymers indeed condense DNA spontaneously, which is a requirement for gene transfer in most types of cells, the physicochemical and biopharmaceutical behavior of the current generation of polyplexes severely limits an efficient gene transfer in vitro and especially in vivo. This paper summarizes recent physicochemical and biological information on polyplexes and aims to provide new insights with respect to this type of gene delivery system. Firstly, the chemical structure of frequently studied cationic polymers is represented. Secondly, the parameters influencing condensation of DNA by cationic polymers are described. Thirdly, the surface properties, solubility, aggregration behavior, degradation and dissociation of polyplexes are considered. The review ends by describing the in vitro and in vivo gene transfection behavior of polyplexes.
引用
收藏
页码:113 / 126
页数:14
相关论文
共 111 条
  • [1] Stability of peptide condensed plasmid DNA formulations
    Adami, RC
    Collard, WT
    Gupta, SA
    Kwok, KY
    Bonadio, J
    Rice, KG
    [J]. JOURNAL OF PHARMACEUTICAL SCIENCES, 1998, 87 (06) : 678 - 683
  • [2] CONDENSATION OF DNA BY TRIVALENT CATIONS .1. EFFECTS OF DNA LENGTH AND TOPOLOGY ON THE SIZE AND SHAPE OF CONDENSED PARTICLES
    ARSCOTT, PG
    LI, AZ
    BLOOMFIELD, VA
    [J]. BIOPOLYMERS, 1990, 30 (5-6) : 619 - 630
  • [3] Synthesis of novel polyampholyte comb-type copolymers consisting of a poly(L-lysine) backbone and hyaluronic acid side chains for a DNA carrier
    Asayama, S
    Nogawa, M
    Takei, Y
    Akaike, T
    Maruyama, A
    [J]. BIOCONJUGATE CHEMISTRY, 1998, 9 (04) : 476 - 481
  • [4] Design of comb-type polyamine copolymers for a novel pH-sensitive DNA carrier
    Asayama, S
    Maruyama, A
    Cho, CS
    Akaike, T
    [J]. BIOCONJUGATE CHEMISTRY, 1997, 8 (06) : 833 - 838
  • [5] Behr JP, 1996, M S-MED SCI, V12, P56
  • [6] 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
    Bielinska, AU
    KukowskaLatallo, JF
    Baker, JR
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1997, 1353 (02): : 180 - 190
  • [7] CONDENSATION OF DNA BY MULTIVALENT CATIONS - CONSIDERATIONS ON MECHANISM
    BLOOMFIELD, VA
    [J]. BIOPOLYMERS, 1991, 31 (13) : 1471 - 1481
  • [8] DNA condensation
    Bloomfield, VA
    [J]. CURRENT OPINION IN STRUCTURAL BIOLOGY, 1996, 6 (03) : 334 - 341
  • [9] Nonviral gene delivery to the rat kidney with polyethylenimine
    Boletta, A
    Benigni, A
    Lutz, J
    Remuzzi, G
    Soria, MR
    Monaco, L
    [J]. HUMAN GENE THERAPY, 1997, 8 (10) : 1243 - 1251
  • [10] A VERSATILE VECTOR FOR GENE AND OLIGONUCLEOTIDE TRANSFER INTO CELLS IN CULTURE AND IN-VIVO - POLYETHYLENIMINE
    BOUSSIF, O
    LEZOUALCH, F
    ZANTA, MA
    MERGNY, MD
    SCHERMAN, D
    DEMENEIX, B
    BEHR, JP
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) : 7297 - 7301