RRC ID |
42017
|
著者 |
Okuda T, Sugiyama A, Niidome T, Aoyagi H.
|
タイトル |
Characters of dendritic poly(L-lysine) analogues with the terminal lysines replaced with arginines and histidines as gene carriers in vitro.
|
ジャーナル |
Biomaterials
|
Abstract |
The development of a non-viral gene delivery system into cells is an important key to realize the safe delivery of therapeutic genes without the side effects often pointed out for viral vectors. We have shown that dendritic poly(L-lysine) of the 6th generation (KG6) shows high transfection efficiency into several cultivated cells with low cytotoxicity. Here, to investigate the effect of substituting terminal cationic groups on the gene delivery into cells, we synthesized KGR6 and KGH6, in which terminal amino acids were replaced by arginines and histidines, respectively. DNA-binding analysis showed that KGR6 could bind to the plasmid DNA as strongly as KG6, whereas KGH6 showed decreased binding ability. KGR6 showed 3- to 12-fold higher transfection efficiency into several cultivated cells than KG6. In contrast, KGH6 showed no transfection efficiency. However, once KGH6 was mixed with the DNA under acidic conditions (pH 5.0), DNA-complexes were formed and they showed high transfection efficiency compared to that in KG6-mediated transfection. DNA-complexes of KGH6 formed under acidic conditions were 1-2 microm and spherical, and relatively stable under neutral conditions. The size and spherical shape of the complexes were the same as those of KG6. The unique character of KGH6 will be one of the basic and valuable tools which will enable us to construct a functional gene transfection system in vitro and in vivo.
|
巻・号 |
25(3)
|
ページ |
537-44
|
公開日 |
2004-2-1
|
DOI |
10.1016/s0142-9612(03)00542-8
|
PII |
S0142961203005428
|
PMID |
14585703
|
MeSH |
Animals
Arginine / chemistry*
CHO Cells
COS Cells
Cations
Cricetinae
DNA / chemistry
Dendrites / metabolism*
Electrophoresis, Agar Gel
Gene Transfer Techniques*
Genetic Vectors
HeLa Cells
Histidine / chemistry*
Humans
Hydrogen-Ion Concentration
Lysine / chemistry*
Microscopy, Fluorescence
Models, Biological
Models, Chemical
Peptides / chemistry
Plasmids / metabolism
Polylysine / chemistry*
Protein Binding
Temperature
Transfection
|
IF |
10.317
|
引用数 |
141
|
WOS 分野
|
ENGINEERING, BIOMEDICAL
MATERIALS SCIENCE, BIOMATERIALS
|
リソース情報 |
ヒト・動物細胞 |
CHO-K1(RCB0285)
COS-7(RCB0539) |