Intracellular signal-responsive artificial gene regulation for novel gene delivery.
We describe two types of artificial gene-regulation systems responding to cyclic AMP-dependent protein kinase (PKA) or caspase-3. These molecular systems use newly synthesized cationic polymers, PAK and PAC. The PAK polymer includes substrate oligopeptide for PKA, ARRASLG, as receptor of PKA signal, while the PAC polymer possesses oligopeptide that is comprised of a substrate sequence of caspase-3, DEVD, and a cationic oligolysine, KKKKKK. These polymers formed stable complexes with DNA to totally suppress the gene expression. However, PKA or caspase-3 signal disintegrates the PAK-DNA or the PAC-DNA complex, respectively. This liberates the DNA and activated the gene expression. These systems are the first concept of an intracellular signal-responsive gene-regulation system using artificial polymer. We expect that these systems can be applied to the novel highly cell specific gene delivery strategy that is involved in our previously proposed new drug delivery concept, the drug delivery system based on responses to cellular signals.
Katayama
Yoshiki
Y
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. ykatatcm@mbox.nc.kyushu-u.ac.jp
Fujii
Kenji
K
Ito
Etsuko
E
Sakakihara
Shigeki
S
Sonoda
Tatsuhiko
T
Murata
Masaharu
M
Maeda
Mizuo
M
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D009842:Oligopeptides / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011355:Prodrugs / Q000378:metabolism; D015398:Signal Transduction; D000099166:Polyacrylamides
D000180:Acrylic Resins; D053148:Caspase 3; D020169:Caspases; D017868:Cyclic AMP-Dependent Protein Kinases; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D009842:Oligopeptides; D011355:Prodrugs; D000099166:Polyacrylamides; C505407:CASP3 protein, human