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 (IFN-γ) 作为治疗蛋白，并开发了几种 IFN-γ 基因治疗系统。选择 IFN-γ 表达载体的适当启动子可调节 IFN-γ 转基因表达的时间曲线。 IFN-γ与调节组织分布的蛋白质融合，导致体内基因转移后IFN-γ的时空控制，这种控制导致基于IFN-γ的基因治疗的治疗效果增加。治疗转移性肿瘤，减少不良反应。

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.

5'-Phosphate oligodeoxynucleotides enhance the phosphodiester-CpG DNA-induced inflammatory response in macrophages

5-磷酸寡脱氧核苷酸增强巨噬细胞中磷酸二酯-CpG DNA 诱导的炎症反应

• DOI: 10.1002/eji.201040396
• 发表时间: 2011
• 期刊: Eur J Immunol
• 影响因子: 5.4
• 作者: Yoshida H;Nishikawa M;Kiyota T;Uno S;Toyota H;Takahashi R;Narita M;Takakura Y.
• 通讯作者: Takakura Y.

Contradictory effects of gene silencing of β-catenin in melanoma cells on proliferation and metastasis (β-catenin 遺伝子発現抑制によるがん細胞増殖抑制効果と転移促進)

黑色素瘤细胞中β-连环蛋白基因沉默对增殖和转移的矛盾影响

• 发表时间: 2009
• 作者: Takahashi Y;et al.
• 通讯作者: et al.

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.

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.