FUNCTIONAL AND TARGETING POLYMERIC GENE CARRIERS

描述（由申请人提供）： 本实验室已开发出非病毒基因传递系统，作为病毒基因传递系统的替代，以克服病毒载体的一些问题。本申请中开发的聚合物基因载体具有作为基因递送材料的优异特性，例如低细胞毒性、中等转染效率、无尺寸限制、操作方便、低成本和可重复性。本文设计了三聚体、水溶性脂聚合物和动脉壁结合肽系统，并将其应用于心肌梗死动物体内的质粒递送。目前已知，移植转染基因的成肌细胞、骨髓细胞和干细胞可显著促进心肌梗死的改善。在这种应用中，一种新的方法是通过基因转移介导的细胞植入来实现治疗性血管生成。构建的生长因子质粒包括VEGF、TGF β 1和PDGF将利用本申请中开发的有效聚合物载体转染到大鼠的成肌细胞、BMC和胚胎干细胞中。预期这些生长因子质粒刺激植入部位的血管生成和生长中的细胞功能。本申请提出了基因递送与细胞工程的结合研究。无论是自体还是异体移植，基因工程细胞的应用都有很大的优势。这些研究结果将为基因工程细胞移植在人类心肌梗死及其他疾病中的应用奠定基础。

DESCRIPTION (provided by applicant): In this laboratory, non viral gene delivery systems have been developed as an alternative for viral gene delivery system to overcome some problems of viral carriers. Polymeric gene carriers developed in this application have excellent characteristics as gene delivery materials such as low cytotoxicity, moderate transfection efficiency, no size limit, convenience of handling, low cost and reproducibility. Terplex, water soluble lipopolymer and artery wall binding peptide systems were designed and characterized in vitro and used for plasmid delivery in myocardial infracted animal. It has been known that transplantation of myoblasts, bone marrow cells and stem cells with transfected genes enhanced significantly the improvement of myocardial infarction. In this application, a novel approach is to achieve therapeutic angiogenesis by cell implantation mediated by gene transfer. Constructed growth factor plasmids including VEGF, TGFbeta1 and PDGF will be transfected in myoblasts, BMC and embryonic stem cells in rats utilizing effective polymer carriers developed in the current application. It is expected that these growth factor plasmids stimulate cell function in angiogenesis and growth at the implanted sites. This application proposes the combined studies between gene delivery and cell engineering. There will be a great advantage for the use of genetically engineered cells either autologus or allogenic transplant. The results obtained from proposed studies will establish criteria for the application of genetically engineered cell implant in the human myocardial infarct and other diseases.