Development of inflammatory cell-specific gene regulation system for gene therapeutic strategy

开发用于基因治疗策略的炎症细胞特异性基因调控系统

• 批准号: 20790042
• 负责人: ASAI Daisuke
• 金额: $ 2.83万
• 依托单位: St.Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790042/
• 关键词: IkappaBkinase; NF-kappaB; 遺伝子キャリアー; ドラッグデリバリー; 遺伝子治療; IkappaB kinase

We proposed a novel strategy called D-RECS (drug or gene delivery system responding to cellular signals) to convert an intracellular signal to transgene expression. Here we apply this concept to inflammatory cells by using Ix-B kinase as a signal molecule that triggers the gene expression. Candidate cationic substrates of Ix-B kinase beta (IKK.(3) were synthesized and their reactivity was investigated. The results of gel shift assay showed that the polyplex was disintegrated and free DNA was released in the presence of IKKf3. The polyplex comprising CMV-GFP plasmid DNA and the polymer expressed the transgene in living cells exposed to a pro-inflammatory stimulus. Our concept of cell-specific gene expression was proved to work in inflammatory cells. This method may provide a unique strategy for gene therapy exclusively in inflammatory cells.

我们提出了一种称为D-RECS（响应细胞信号的药物或基因递送系统）的新策略，将细胞内信号转化为转基因表达。在这里，我们通过使用Ix-B激酶作为触发基因表达的信号分子，将这一概念应用于炎症细胞。Ix-B激酶β（IKK. (3)并对其反应活性进行了研究。凝胶迁移实验结果表明，IKKf 3作用后，复合物被降解，释放出游离DNA。包含CMV-GFP质粒DNA和聚合物的多聚物在暴露于促炎刺激的活细胞中表达转基因。我们的细胞特异性基因表达的概念被证明在炎症细胞中起作用。这种方法可能提供一种独特的策略，专门在炎症细胞的基因治疗。

项目成果

Specific transgene expression in virus-infected cells by a virus protease-cleavable transcription suppressor

病毒蛋白酶可裂解的转录抑制因子在病毒感染的细胞中特异性转基因表达

• 发表时间: 2009
• 作者: Asai;D.;et al.
• 通讯作者: et al.

Tumor intracellular signal-targeting by application of specific substrate peptide for protein kinasecc

应用蛋白激酶特异性底物肽靶向肿瘤细胞内信号cc

• 发表时间: 2008
• 作者: Asai;D.;Knag;J.H.;Toita;R.;Tomiyama;T.;Mori;T.;Niidome;T.;Nakashima;H.;Katayama;Y.
• 通讯作者: Y.

ウイルス感染細胞選択的な遺伝子発現制御システムの構築

病毒感染细胞选择性基因表达控制系统的构建

• 发表时间: 2008
• 作者: 倉本政則;ほか
• 通讯作者: ほか

Plasma protein kinase C (PKC)α as a biomarker for the diagnosis of cancers

• DOI: 10.1093/carcin/bgp210
• 发表时间: 2009-11-01
• 期刊: CARCINOGENESIS
• 影响因子: 4.7
• 作者: Kang, Jeong-Hun;Asai, Daisuke;Katayama, Yoshiki
• 通讯作者: Katayama, Yoshiki

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

使用蛋白酶可裂解转录调节因子在 HIV 感染细胞中进行特异性转基因表达。

• 发表时间: 2010
• 期刊: J Control. Release 141
• 作者: Asai;D.;Kuramoto;M.;Shoji;Y.;Kang;J.H.;Kodama;B.K.;Kawamura;K.;Mori;T.;Miyoshi;H.;Niidome;T.;Nakashima;H.;Katayama;Y.
• 通讯作者: Y.