RRC ID |
42501
|
Author |
Oishi J, Kawamura K, Kang JH, Kodama K, Sonoda T, Murata M, Niidome T, Katayama Y.
|
Title |
An intracellular kinase signal-responsive gene carrier for disordered cell-specific gene therapy.
|
Journal |
J Control Release
|
Abstract |
We have previously reported artificial gene-regulation systems responding to cyclic AMP-dependent protein kinase (PKA) using cationic polymer. This cationic polymer (PAK) was a graft-type polymer with an oligopeptide that is a substrate for PKA and could regulate gene-expression in a cell-free system. In the present study, we carried out a detailed characterization of the PAK-DNA complex (AFM observation and DLS measurement) and tried to apply this polymer to living cells. In the unstimulated NIH 3T3 cells, transfection of the PAK-DNA complex showed no expression of the delivered gene. This means that PAK formed a stable complex with DNA in the normal cells to totally suppress gene expression. In contrast, significant expression was seen when the PAK-DNA complex was delivered to forskolin-treated cells. Thus, activated PKA disintegrates the complexes even in living cells, resulting in gene expression. Our results indicate that this type of intracellular signal-responsive polymer will be useful for the cell-specific release of genes.
|
Volume |
110(2)
|
Pages |
431-436
|
Published |
2006-1-10
|
DOI |
10.1016/j.jconrel.2005.10.007
|
PII |
S0168-3659(05)00530-4
|
PMID |
16309776
|
MeSH |
3T3 Cells
Adenosine Triphosphate / chemistry
Animals
Cyclic AMP-Dependent Protein Kinases / genetics*
Cyclic AMP-Dependent Protein Kinases / metabolism
DNA / biosynthesis
DNA / genetics
Drug Carriers*
Genes, Reporter
Genetic Therapy / methods*
Green Fluorescent Proteins / genetics
Light
Luciferases / genetics
Mice
Microscopy, Atomic Force
Peptides / chemistry
Peptides / metabolism
Phosphorylation
Polymers / chemical synthesis
Scattering, Radiation
Tetrazolium Salts / chemistry
|
IF |
7.727
|
Times Cited |
42
|
WOS Category
|
PHARMACOLOGY & PHARMACY
CHEMISTRY, MULTIDISCIPLINARY
|
Resource |
Human and Animal Cells |
NIH/3T3 |