TY - JOUR
T1 - Transgene regulation system responding to Rho associated coiled-coil kinase (ROCK) activation
AU - Tsuchiya, Akira
AU - Kang, Jeong Hun
AU - Asai, Daisuke
AU - Mori, Takeshi
AU - Niidome, Takuro
AU - Katayama, Yoshiki
N1 - Funding Information:
This work was financially supported by a grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture in Japan and also supported by A3 Foresight Program in Japan Society for the Promotion of Science . A. T. is grateful to Japan Society for the Promotion of Science (JSPS) for the DC scholarship.
PY - 2011/10/10
Y1 - 2011/10/10
N2 - Recently, we have proposed a new system of gene regulation called 'drug or gene delivery system responding to cellular signals' (D-RECS). In this system, transgene expression is activated in response to intracellular target protein kinases or proteases for safe, cell-specific gene delivery by using peptide-polymer conjugates. Here we applied this system to an intracellular Rho-associated coiled-coil kinase (ROCK) signal, which is activated abnormally in cardiovascular diseases. A ROCK responsive polymer consisting of neutral polymers in main chain and cationic ROCK substrate peptides in side chains was prepared and could form the complex with plasmid DNA. The complex was transferred into NIH3T3 cells with or without L-α-lysophosphatidic acid (LPA) that increases ROCK activity. At an N/P ratio of 2.0, a significant increase of the gene expression was identified in LPA-treated NIH3T3 cells, but was disappeared in NIH3T3 cells treated with ROCK specific inhibitor, Y-27632. These results suggest that the ROCK responsive polymer can regulate gene expression in response to ROCK activity.
AB - Recently, we have proposed a new system of gene regulation called 'drug or gene delivery system responding to cellular signals' (D-RECS). In this system, transgene expression is activated in response to intracellular target protein kinases or proteases for safe, cell-specific gene delivery by using peptide-polymer conjugates. Here we applied this system to an intracellular Rho-associated coiled-coil kinase (ROCK) signal, which is activated abnormally in cardiovascular diseases. A ROCK responsive polymer consisting of neutral polymers in main chain and cationic ROCK substrate peptides in side chains was prepared and could form the complex with plasmid DNA. The complex was transferred into NIH3T3 cells with or without L-α-lysophosphatidic acid (LPA) that increases ROCK activity. At an N/P ratio of 2.0, a significant increase of the gene expression was identified in LPA-treated NIH3T3 cells, but was disappeared in NIH3T3 cells treated with ROCK specific inhibitor, Y-27632. These results suggest that the ROCK responsive polymer can regulate gene expression in response to ROCK activity.
UR - http://www.scopus.com/inward/record.url?scp=80053307321&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053307321&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2011.05.002
DO - 10.1016/j.jconrel.2011.05.002
M3 - Article
C2 - 21586308
AN - SCOPUS:80053307321
SN - 0168-3659
VL - 155
SP - 40
EP - 46
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -
