Design and delivery of plasmid vector for spatiotemporal control of the expression of therapeutic protein and siRNA

用于时空控制治疗蛋白和 siRNA 表达的质粒载体的设计和递送

• 批准号: 21390009
• 负责人: TAKAKURA Yoshinobu
• 金额: $ 11.73万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390009/
• 关键词: ドラッグデリバリー; 遺伝子治療; RNA干渉; プラスミドDNA; 融合タンパク質; デリバリー

Interferon-γ(IFN-γ) was selected as a therapeutic protein and several IFN-γgene therapy systems were developed. Selection of proper promoters of IFN-γ-expressing vectors resulted in the regulation of the time profile of IFN-γtransgene expression. A fusion of IFN-γwith a protein that regulates the tissue distribution resulted in the spatiotemporal control of IFN-γafter in vivo gene transfer. This control led to an increase in the therapeutic effect of IFN-γ-based gene therapy on metastatic tumor with reduction in adverse effects.

选择干扰素-γ(干扰素-γ)作为治疗性蛋白，建立了几种干扰素-γ基因治疗系统。选择合适的干扰素-γ表达载体启动子可以调节干扰素-γ转基因表达的时间分布。在体内基因转移后，干扰素-γ与调节组织分布的蛋白质的融合导致了干扰素-γ的时空调控。这一对照提高了以干扰素-γ为基础的基因治疗转移性肿瘤的疗效，同时减少了不良反应。

项目成果

Enhanced CTL response by controlled intracellular trafficking of antigen in dendritic cells following DNA vaccination

DNA 疫苗接种后，通过控制树突状细胞中抗原的细胞内运输来增强 CTL 反应

• DOI: 10.1016/j.jconrel.2009.01.026
• 发表时间: 2009
• 期刊: J Control Release
• 影响因子: 10.8
• 作者: Isaji K;Kawase A;Matono M;Guan X;Nishikawa M;Takakura Y.
• 通讯作者: Takakura Y.

Interferonγ-mediated inhibition of nuclear entry of plasmid vector and mRNA transcription from the vector : an obstacle for repeated injections of interferonγ-expressing plasmid vector

干扰素γ介导的质粒载体入核和载体mRNA转录的抑制：重复注射干扰素γ表达质粒载体的障碍

• 发表时间: 2010
• 作者: Zang L;Nishikawa M;Machida K;Ando M;Takahashi Y;Takakura Y.
• 通讯作者: Takakura Y.

Interferon γ-mediated inhibition of nuclear entry of plasmid vector and mRNA transcription from the vector:an obstacle for repeated injections of interferon γ-expressing plasmid vector.

干扰素γ介导的对质粒载体入核和载体mRNA转录的抑制：重复注射干扰素γ表达质粒载体的障碍。

• 发表时间: 2010
• 作者: Zang L.;et al.
• 通讯作者: et al.

Inhibition of nuclear delivery of plasmid DNA and transcription by interferonγ: hurdles to be overcome for sustained gene therapy

干扰素γ抑制质粒DNA的核递送和转录：持续基因治疗需要克服的障碍

• DOI: 10.1038/gt.2011.35
• 发表时间: 2011
• 期刊: Gene Ther
• 影响因子: 5.1
• 作者: Zang L;Nishikawa M;Machida K;AndoM;Takahashi Y;Watanabe Y;Takakura Y.
• 通讯作者: Takakura Y.

Design and gene delivery of mouse interferonγgenetically fused with mouse serum albumin

小鼠干扰素γ与小鼠血清白蛋白基因融合的设计和基因传递

• 发表时间: 2010
• 作者: Miyakawa N;Nishikawa M;Takahashi Y;Watanabe Y;Takakura Y.
• 通讯作者: Takakura Y.