[Gene delivery system responding to the intracellular signal].
We designed a peptide-polymer conjugate as a novel gene carrier, which could control gene-expression responding to intracellular cAMP-dependent protein kinase (PKA) or caspase-3 signal. Each polymer containing a substrate peptide (ALRRASLG for PKA or GGGDEVD GGRKKRRQRRRPPQ for caspase-3) could form a tight complex with plasmid DNA via electrostatic interaction, and in this state, the gene expression was totally suppressed. Once the grafted peptides become phosphorylated or hydrolyzed by the appropriate enzyme, the net charge of the peptide changes from cationic to neutral or anionic, respectively, and the polymer then releases the DNA, such that expression of the foreign gene should become activated. We expect that these systems can be applied to the novel highly cell specific gene delivery strategy.
Kawamura
Kenji
K
Department of Applied Chemistry, Faculty of Engineering, Kyushu University.
Katayama
Yoshiki
Y
D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000493:pharmacokinetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D018014:Gene Transfer Techniques; D015398:Signal Transduction
D017868:Cyclic AMP-Dependent Protein Kinases; D053148:Caspase 3; D020169:Caspases