Molecular mechanism of caspase-3-induced gene expression of polyplexes formed from polycations grafted with cationic substrate peptides.
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.
Kawamura
Kenji
K
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka Nishi-ku, Fukuoka 819-0395, Japan.
Kuramoto
Masanori
M
Mori
Takeshi
T
Toita
Riki
R
Oishi
Jun
J
Sato
Yuko
Y
Kang
Jeong-Hum
JH
Asai
Daisuke
D
Niidome
Takuro
T
Katayama
Yoshiki
Y
D000180:Acrylic Resins / Q000737:chemistry*; D000595:Amino Acid Sequence; D053148:Caspase 3 / Q000378:metabolism* / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D000099166:Polyacrylamides
D000180:Acrylic Resins; D053148:Caspase 3; D010455:Peptides; D000099166:Polyacrylamides