喉鳞癌特异、双重靶向基因治疗的实验研究

项目名称： 喉鳞癌特异、双重靶向基因治疗的实验研究

项目编号： No.30872850

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 刘世喜

作者单位： 四川大学

项目金额： 32万元

中文摘要： 近年来, 随着肿瘤分子生物学的发展，有关肿瘤基因治疗的研究取得了较大的进展，但是在喉鳞癌基因治疗的研究过程中出现了影响其有效性和特异性发挥的"瓶颈"。本课题正是以此为出发点，从喉鳞癌噬菌体单链抗体库入手，通过先进的体内筛选技术构建特异靶向喉鳞癌细胞的AAV2载体，并将此AAV2载体应用于与喉鳞癌密切相关的Livin基因。对体外培养的鳞癌细胞和已建立的喉癌动物模型进行完全随机对照实验，来系统地观察Livin shRNA-rAAV2在提高细胞靶向的前提下，能否使目的基因长期稳定地表达。以期从细胞水平和基因水平双重靶向的角度来提高喉鳞癌基因治疗的有效性、特异性和靶向性，从而突破当前肿瘤基因治疗的"瓶颈"，为今后喉鳞癌的特异、双重靶向基因治疗方案开辟一条新途径，并为其他肿瘤基因治疗带来新的思维和突破。

中文关键词： 喉鳞癌；靶向；基因治疗；噬菌体；腺相关病毒

英文摘要： In recent years, with the development of cancer molecular biology, cancer gene therapy investigation has made great progress, but the "bottleneck"was appeared to influence the validity and specificity on the process of laryngeal cancer gene therapy research .The subject was based this goal. From phage display single-chain antibody library as the start,This aimed at to construct AAV2 vector that targeted and specfic to the cell of the larygeal squamous carcinoma ,through advanced panning technology in vivo,and this vectors will be applied to Livin gene related with laryngeal squamous cell carcinoma closely.We will utilize the random-controlled experiments by squamous carcinoma cells and animal model of larygeal carcinoma to observe systematically whether Livin shRNArAAV2 make stable gene expression in the long-term to increase the ability of targeted cells.The goal of research want that increase the validity、specificity and targeted of laryngeal cancer gene therapy to break through the "bottleneck"in cell and gene level in the current cancer gene therapy.It will open up a new way to the double Targeted gene therapy programme and bring new ideas and breakthroughs for other cancer gene therapy in the future.

英文关键词： phage display;adeno-associated virus; AAV;Livin ;gene therapy;laryngeal cancer.