An intracellular kinase signal-responsive gene carrier for disordered cell-specific gene therapy

Jun Oishi, Kenji Kawamura, Jeong Hun Kang, Kota Kodama, Tatsuhiko Sonoda, Masaharu Murata, Takuro Niidome, Yoshiki Katayama

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

We have previously reported artificial gene-regulation systems responding to cyclic AMP-dependent protein kinase (PKA) using cationic polymer. This cationic polymer (PAK) was a graft-type polymer with an oligopeptide that is a substrate for PKA and could regulate gene-expression in a cell-free system. In the present study, we carried out a detailed characterization of the PAK-DNA complex (AFM observation and DLS measurement) and tried to apply this polymer to living cells. In the unstimulated NIH 3T3 cells, transfection of the PAK-DNA complex showed no expression of the delivered gene. This means that PAK formed a stable complex with DNA in the normal cells to totally suppress gene expression. In contrast, significant expression was seen when the PAK-DNA complex was delivered to forskolin-treated cells. Thus, activated PKA disintegrates the complexes even in living cells, resulting in gene expression. Our results indicate that this type of intracellular signal-responsive polymer will be useful for the cell-specific release of genes.

Original languageEnglish
Pages (from-to)431-436
Number of pages6
JournalJournal of Controlled Release
Volume110
Issue number2
DOIs
Publication statusPublished - Jan 10 2006

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'An intracellular kinase signal-responsive gene carrier for disordered cell-specific gene therapy'. Together they form a unique fingerprint.

  • Cite this