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.
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