用于间充质干细胞的高分子基因载体的设计制备和抗肿瘤治疗研究

项目名称： 用于间充质干细胞的高分子基因载体的设计制备和抗肿瘤治疗研究

项目编号： No.21474104

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 田华雨

作者单位： 中国科学院长春应用化学研究所

项目金额： 88万元

中文摘要： 骨髓间充质干细胞具有较强的肿瘤组织靶向趋化侵入能力、低的免疫原性以及易于体外大量培养等特点，因此人们把可表达肿瘤杀伤因子的间充质干细胞导入体内进行抗肿瘤靶向治疗。利用非病毒基因载体转染干细胞表达肿瘤杀伤因子比使用病毒载体更加安全可靠，但常用的非病毒基因载体细胞毒性大、转染效率低。制备低毒高效的干细胞非病毒基因载体是推动干细胞在基因治疗领域应用的关键。本项目设计了具有不同电荷密度、不同亲疏水氨基酸构成以及不同拓扑结构的可降解聚氨基酸基因载体，以探索具有不同分子结构的基因载体对骨髓间充质干细胞转染性能的影响，找到适用于干细胞的基因载体设计规则，筛选出适用于间充质干细胞的基因载体。利用该类载体将治疗基因导入骨髓间充质干细胞，得到可表达肿瘤杀伤因子的骨髓间充质干细胞，并将其导入乳腺癌肺转移瘤模型动物体内进行抗肿瘤治疗。通过多种检测手段评价治疗效果，建立骨髓间充质干细胞的体内基因治疗方案。

中文关键词： 基因载体；间充质干细胞；肿瘤治疗；基因治疗

英文摘要： With the advantages of tumor targeting invading capacity, low immunogenicity and ease to be proliferated in vitro, genic recombined mesenchymal stem cells which could express tumor necrosis factors are considered to be new strategies for tumor targeting therapy. Although nonviral gene carriers are considered to be more secure in in vivo applications of mesenchymal stem cells than viral gene carriers, their high cytotoxicity and low gene transfection efficiency hinder their in vivo application. To prepare nonviral gene carriers for stem cells with low cytotoxicity and high transfection efficiency is the key for further applications of stem cells-based gene therapy. In this project, a series of poly(amino acid)-based gene carriers with different charge density, different composition of hydrophilic and hydrophobic amino acid and different topological structure is designed to investigate the relationships between the structure and their transfection efficiency to mesenchymal stem cells, and to prepare a series of poly(amino acid)-based gene carriers for stem cells transfection. Further study will be focused on obtaining genic recombined mesenchymal stem cells which could express tumor necrosis factors by transfected with these gene carriers. The anti-tumor therapeutic effect mediated by these genic recombined mesenchymal stem cells in animal models of lung metastases from breast cancer will be evaluated with a variety of methods. And the mesenchymal stem cells-based gene therapy programme will be eventually established.

英文关键词： gene carriers;mesenchymal stem cells;cancer therapy;gene therapy