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 7.901
Times Cited 42
WOS Category PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY
Resource
Human and Animal Cells