Intracellular signal-responsive artificial gene regulation for novel gene delivery

被引:43
作者
Katayama, Y [1 ]
Fujii, K [1 ]
Ito, E [1 ]
Sakakihara, S [1 ]
Sonoda, T [1 ]
Murata, M [1 ]
Maeda, M [1 ]
机构
[1] Kyushu Univ, Fac Engn, Dept Appl Chem, Higashi Ku, Fukuoka 8128581, Japan
关键词
D O I
10.1021/bm025532h
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:905 / 909
页数:5
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