Molecular mechanism of caspase-3-induced gene expression of polyplexes formed from polycations grafted with cationic substrate peptides

Kenji Kawamura, Masanori Kuramoto, Takeshi Mori, Riki Toita, Jun Oishi, Yuko Sato, Jeong Hum Kang, Daisuke Asai, Takuro Niidome, Yoshiki Katayama

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)967-980
    Number of pages14
    JournalJournal of Biomaterials Science, Polymer Edition
    Volume20
    Issue number7-8
    DOIs
    Publication statusPublished - Apr 1 2009

    All Science Journal Classification (ASJC) codes

    • Biophysics
    • Bioengineering
    • Biomaterials
    • Biomedical Engineering

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