TY - JOUR
T1 - Molecular mechanism of caspase-3-induced gene expression of polyplexes formed from polycations grafted with cationic substrate peptides
AU - Kawamura, Kenji
AU - Kuramoto, Masanori
AU - Mori, Takeshi
AU - Toita, Riki
AU - Oishi, Jun
AU - Sato, Yuko
AU - Kang, Jeong Hum
AU - Asai, Daisuke
AU - Niidome, Takuro
AU - Katayama, Yoshiki
N1 - Funding Information:
This work was supported by the New Energy and Industrial Technology (NEDO), CREST from the Japan Science and Technology Agency, and a Grant-in-Aid for Scientific Research form the Japanese Ministry of Education, Culture, Sports, Science and Technology (No. 19650125).
PY - 2009/4/1
Y1 - 2009/4/1
N2 - We previously reported a novel disease-site-specific gene targeting system that can release plasmid DNA (pDNA) from polymeric carriers responding to abnormally activated signal proteins in disease cells. In this study, the molecular mechanism of the gene targeting system responding to Caspase-3 activity was studied in detail. The polymeric carrier used was composed of a neutral main chain polymer and a grafted oligocationic peptide which contains the substrate sequence of Caspase-3. The polyplex formed from the polymeric carrier and pDNA was stable in physiological saline solution and protected from access of RNA polymerase and the transcriptional factors. These results indicate that the polyplex adopts a core-shell-like structure with a polyion complex core surrounded by neutral main chain polymers. In spite of the inert character of the polyplex to transcription, the polyplex afforded the access of Caspase-3 to the substrate peptide because the electrostatic interaction between each peptide and DNA is essentially weak. After the Caspase-3 reaction, the polyplex was weakened and then became available as a template for transcription.
AB - We previously reported a novel disease-site-specific gene targeting system that can release plasmid DNA (pDNA) from polymeric carriers responding to abnormally activated signal proteins in disease cells. In this study, the molecular mechanism of the gene targeting system responding to Caspase-3 activity was studied in detail. The polymeric carrier used was composed of a neutral main chain polymer and a grafted oligocationic peptide which contains the substrate sequence of Caspase-3. The polyplex formed from the polymeric carrier and pDNA was stable in physiological saline solution and protected from access of RNA polymerase and the transcriptional factors. These results indicate that the polyplex adopts a core-shell-like structure with a polyion complex core surrounded by neutral main chain polymers. In spite of the inert character of the polyplex to transcription, the polyplex afforded the access of Caspase-3 to the substrate peptide because the electrostatic interaction between each peptide and DNA is essentially weak. After the Caspase-3 reaction, the polyplex was weakened and then became available as a template for transcription.
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U2 - 10.1163/156856209X444376
DO - 10.1163/156856209X444376
M3 - Article
C2 - 19454163
AN - SCOPUS:67649204828
VL - 20
SP - 967
EP - 980
JO - Journal of Biomaterials Science, Polymer Edition
JF - Journal of Biomaterials Science, Polymer Edition
SN - 0920-5063
IS - 7-8
ER -