Effects On Proliferation Of Vascular Smooth Muscle Cells By Coexpressing CD/TK Double Suicide Genes

Gene therapy is regarded as a potential revolution in medicine and its prospect is attractive. The first decade of gene therapy has passed. However, the results on the clinical trials were disappointed mainly because of the insufficient gene transfer efficiency and low expression levels of foreign genes. It's a goal to search for effective clinical approaches that can resolves the addressing difficulties.Study on restenosis after angioplasty is a topic of general interests because of its high incidence and local pathological changes. The proliferation and migration of vascular smooth muscle cells (VSMCs) are one of the fundamental mechanisms of restenosis , thus VSMCs become the most important target. The treatment to inhibit the proliferation of VSMCs was showed to reduce the incidence of restenosis.It's a trend towards achieving antiproliferation effect on VSMCs by suicide gene therapy. The most intensively studied strategies involve HSV-tk/GCV and CD/5-Fc systems. But their curative effects also need to be enhanced in order to approach clinical application. For the two systems inhibiting VSMCs via different mechanisms, so in an attempt to increase the expression levels of the foreign genes, improve the current curative effect and provide an effective technology to inhibit VSMC by suicide gene therapy, the research work employs coexpressing of HSV-TK and CD by designing multicistronic nonviral or adenoviral vectors. The present studies are as follows:1 The vector constructions, steady expressions and antiproliferation effects of CD and/or TK suicide genes on target cells: Recombinant eukaryotic plasmid vectors namely pcDNA3-TK pcDNA3-CD pcDNA3-TK-CD under CMV promoters were constructed successfully. The vectors were introduced to GLC-82 tumor cell lines and Rat VSMCs with lipofectamine. The steady expression clones...