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Development of real-time intracellular pH sensor using a membrane-permeable peptide nucleic acid.

使用膜渗透性肽核酸开发实时细胞内 pH 传感器。

基本信息

批准号：
16500200
负责人：
TOMIZAWA Kazuhito
金额：
$ 2.37万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Membrane-permeable peptide nucleic acid (PNA) developed by us is thought to be a powerful tool for the regulation of cell function. The purpose of this project is that development of the tools that are useful for the regulation of protein expression and the function and for the monitoring of nano-ecology in living cells using the PNA. In the present project, we show that membrane-permeable PNA is a powerful tool for the regulation of gene expression and for anti-cancer therapy as follows.1.Regulation of gene expression.We synthesized a PNA, which effectively hybridized with plasmid DNA, and the PNA was fused a membrane-permeable poly-arginine to have the ability of membrane permeability. After mixing the PNA with plasmid DNAs, cells were incubated with the complex and the efficiency of the transfection was investigated. The plasmid DNAs were effectively transfected in both cells and the efficiency is better than that of cationic transfection method.2.Antigene therapy using membrane-permeable PNA.We synthesized PNAs that are able to bind with p53 mRNA and the double-strand DNA. Cancer cells were incubated with the PNAs. The PNAs were delivered into cells and inhibited the expression of p53 mRNA and the protein. The combination treatment of the PNAs with p53 protein therapy was capable to replace endogenous mutated p53 proteins with wild-type p53 proteins in the cancer cells.

我们开发的透膜肽核酸（PNA）被认为是调节细胞功能的有力工具。该项目的目的是开发可用于调节蛋白质表达和功能以及使用 PNA 监测活细胞中纳米生态的工具。在本项目中，我们证明了膜渗透性PNA是调节基因表达和抗癌治疗的有力工具，具体如下：1.基因表达的调节。我们合成了一种PNA，它与质粒DNA有效杂交，并与膜渗透性聚精氨酸融合，使其具有膜渗透能力。将 PNA 与质粒 DNA 混合后，将细胞与复合物一起孵育并研究转染效率。质粒DNA在两种细胞中均得到有效转染，效率优于阳离子转染法。2.透膜PNA抗原治疗。我们合成了能够与p53 mRNA和双链DNA结合的PNA。癌细胞与 PNA 一起孵育。 PNA 被递送到细胞中并抑制 p53 mRNA 和蛋白质的表达。 PNA 与 p53 蛋白疗法的联合治疗能够在癌细胞中用野生型 p53 蛋白替代内源突变的 p53 蛋白。

项目成果

期刊论文数量（56）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

p53 protein transduction therapy: Successful targeting and inhibition of the growth of the bladder cancer cells

DOI：
10.1016/j.eururo.2005.08.019
发表时间：
2006-01-01
期刊：
EUROPEAN UROLOGY
影响因子：
23.4
作者：
Inoue, M;Tomizawa, K;Matsui, H
通讯作者：
Matsui, H

タンパク質セラピー法

蛋白质疗法

DOI：
发表时间：
2004
期刊：
実験医学 Vol.22・No.18
影响因子：
0
作者：
松下正之;富澤一仁;松井秀樹
通讯作者：
松井秀樹

Regulation of synaptic vesicle recycling by calcineurin in different vesicle pools

DOI：
10.1016/j.neures.2004.12.018
发表时间：
2005-04-01
期刊：
NEUROSCIENCE RESEARCH
影响因子：
2.9
作者：
Kumashiro, S;Lu, YF;Matsui, H
通讯作者：
Matsui, H

The NH2-terminal of influenza virus hemagglutinin-2 subunit peptides enhance the anti-tumor potency of poly-arginine-mediated p53 protein transduction.

流感病毒血凝素 2 亚基肽的 NH2 末端增强聚精氨酸介导的 p53 蛋白转导的抗肿瘤效力。

DOI：
发表时间：
2005
期刊：
J.Biol.Chem. 280(9)
影响因子：
0
作者：
Michiue H;Tomizawa K;Wei FY;Matsushita M;Lu YF;Ichikawa T;Tamiya T;Date I;Matsui H.
通讯作者：
Matsui H.

Control of cyclin‐dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability

DOI：
10.1111/j.1471-4159.2005.03058.x
发表时间：
2005-04
期刊：
Journal of Neurochemistry
影响因子：
4.7
作者：
Fan-Yan Wei;K. Tomizawa;T. Ohshima;A. Asada;Taro Saito;C. Nguyen;J. Bibb;K. Ishiguro;Ashok B Kulkarni;H. Pant;K. Mikoshiba;H. Matsui;S. Hisanaga
通讯作者：
Fan-Yan Wei;K. Tomizawa;T. Ohshima;A. Asada;Taro Saito;C. Nguyen;J. Bibb;K. Ishiguro;Ashok B Kulkarni;H. Pant;K. Mikoshiba;H. Matsui;S. Hisanaga