Specific transgene expression in HIV-infected cells using protease-cleavable transcription regulator

Daisuke Asai, Masanori Kuramoto, Yoko Shoji, Jeong Hun Kang, Kota Bae Kodama, Kenji Kawamura, Takeshi Mori, Hiroshi Miyoshi, Takuro Niidome, Hideki Nakashima, Yoshiki Katayama

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)


    Gene therapy is a promising strategy for the treatment of HIV infection, but cell specificity remains an issue. Recently we have developed a new concept for a drug or gene delivery system responding to cellular signals (D-RECS) to achieve cell-specific transgene expression using a non-viral polymer-based vehicle. According to this concept, intracellular signaling enzymes, which are activated specifically in target cells, are used to trigger transgene expression. We previously applied this concept to HIV-1 protease and showed that the recombinant protease could act as a suitable signal. Here we further developed this system to achieve highly specific transgene expression in HIV-infected cells. We prepared a polymeric gene regulator grafted with a cationic peptide containing the HIV-Tat peptide via a specific substrate for HIV-1 protease. The regulator formed a stable polyplex with the transgene, suppressing its transcription. HIV-1 protease cleaved the peptide and released the transgene, which was consequently expressed specifically in activated HIV-infected cells, but remained unreleased and inactive in uninfected cells. The validity of this approach was further confirmed by applying it to the CVB1 2A protease of coxsackievirus (Picornaviridae family). This strategy should be widely applicable for specific expression of a variety of therapeutic genes in virus-infected cells.

    Original languageEnglish
    Pages (from-to)52-61
    Number of pages10
    JournalJournal of Controlled Release
    Issue number1
    Publication statusPublished - Jan 4 2010

    All Science Journal Classification (ASJC) codes

    • Pharmaceutical Science


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