| RRC ID |
42790
|
| 著者 |
Yamagata M, Kawano T, Shiba K, Mori T, Katayama Y, Niidome T.
|
| タイトル |
Structural advantage of dendritic poly(L-lysine) for gene delivery into cells.
|
| ジャーナル |
Bioorg Med Chem
|
| Abstract |
This study aimed to investigate the relationships between structures of gene carrier molecules and their activities for gene delivery into cells. We compared 2 types of poly(L-lysine) as carriers, that is, dendritic poly(L-lysine) (KG6) and linear poly(L-lysine) (PLL). KG6 formed a neutral DNA complex, and its DNA compaction level was weaker than that of PLL. The amount of DNA binding and uptake into cells mediated by PLL was 4-fold higher than that with KG6. However, KG6-mediated gene expression was 100-fold higher than that by PLL. Since pK(a) values of terminal amines of KG6 were lowered even though small amounts of DNA were internalized into cells, sufficient DNA amounts for effective gene expression escaped to the cytosol due to the proton sponge effect in the endosome. In addition, weakly compacted DNA with KG6 was advantageous in accessing RNA polymerase in the cell nucleus. On the other hand, PLL did not show the proton sponge effect in the endosome and resulted in strong compaction of DNA. Even though large DNA amounts were internalized into cells, most of the DNA would not take part in gene expression systems in the nucleus. Amount of induced cytokine production after intravenous injection of DNA complexes with KG6 and PLL was low, and was similar to the case when DNA was injected alone. Therefore, no significant difference in effects on cytokine production was observed between KG6 and PLL.
|
| 巻・号 |
15(1)
|
| ページ |
526-32
|
| 公開日 |
2007-1-1
|
| DOI |
10.1016/j.bmc.2006.09.033
|
| PII |
S0968-0896(06)00764-4
|
| PMID |
17035030
|
| MeSH |
Animals
Binding Sites
CHO Cells
Cells, Cultured
Cricetinae
Cytokines / pharmacology
DNA / chemistry
DNA / drug effects
Dendrimers / chemistry*
Gene Expression Regulation, Enzymologic / drug effects
Gene Transfer Techniques*
Luciferases / drug effects
Luciferases / genetics
Molecular Structure
Polylysine / chemistry*
Structure-Activity Relationship
|
| IF |
3.073
|
| 引用数 |
100
|
|
WOS 分野
|
CHEMISTRY, MEDICINAL
CHEMISTRY, ORGANIC
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
CHO-K1(RCB0285) |
