TY - JOUR
T1 - An intracellular kinase signal-responsive gene carrier for disordered cell-specific gene therapy
AU - Oishi, Jun
AU - Kawamura, Kenji
AU - Kang, Jeong Hun
AU - Kodama, Kota
AU - Sonoda, Tatsuhiko
AU - Murata, Masaharu
AU - Niidome, Takuro
AU - Katayama, Yoshiki
N1 - Funding Information:
This work was financially supported by CREST, the Japan Science Corp., a grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture in Japan, and a grant-in-aid for Scientific Research from the Ministry of Health, Labour, and Welfare.
PY - 2006/1/10
Y1 - 2006/1/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jconrel.2005.10.007
DO - 10.1016/j.jconrel.2005.10.007
M3 - Article
C2 - 16309776
AN - SCOPUS:29244432184
SN - 0168-3659
VL - 110
SP - 431
EP - 436
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -