抄録
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.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 52-61 |
| ページ数 | 10 |
| ジャーナル | Journal of Controlled Release |
| 巻 | 141 |
| 発行部数 | 1 |
| DOI | |
| 出版物ステータス | 出版済み - 1 4 2010 |
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All Science Journal Classification (ASJC) codes
- Pharmaceutical Science
これを引用
Specific transgene expression in HIV-infected cells using protease-cleavable transcription regulator. / Asai, Daisuke; Kuramoto, Masanori; Shoji, Yoko; Kang, Jeong Hun; Kodama, Kota Bae; Kawamura, Kenji; Mori, Takeshi; Miyoshi, Hiroshi; Niidome, Takuro; Nakashima, Hideki; Katayama, Yoshiki.
：: Journal of Controlled Release, 巻 141, 番号 1, 04.01.2010, p. 52-61.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Specific transgene expression in HIV-infected cells using protease-cleavable transcription regulator
AU - Asai, Daisuke
AU - Kuramoto, Masanori
AU - Shoji, Yoko
AU - Kang, Jeong Hun
AU - Kodama, Kota Bae
AU - Kawamura, Kenji
AU - Mori, Takeshi
AU - Miyoshi, Hiroshi
AU - Niidome, Takuro
AU - Nakashima, Hideki
AU - Katayama, Yoshiki
PY - 2010/1/4
Y1 - 2010/1/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70849106158&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70849106158&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2009.08.025
DO - 10.1016/j.jconrel.2009.08.025
M3 - Article
C2 - 19733602
AN - SCOPUS:70849106158
VL - 141
SP - 52
EP - 61
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -