Gene therapy for cancer with retrovirus vectors. Testing of vectors with tumor necrosis factor and vectors with siRNA expression cassette.
Project leader: KristĂna Hlubinová
Project duration: 2006 - 2008
Proposed project is a continuation our previous work with improvement of retrovirus vectors for gene therapy. We intend to test these bicistronic vectors containing thymidine kinase of Herpes simplex virus, gene of neomycine resistance and siRNA expression cassette used for blocking of three different caspases (caspase 2, caspase 3, caspase 8),thus providing inhibition of different apoptic pathways in tested cells.
We plan to test the application of human tumor necrosis factor alpha therapeutic gene, the product of this gene is protein- cytokine, which is an effective inducer of apoptosis. That why we prepare a new retroviral vector with TNF-alpha gene under the radiation-inducible promoter egr-1. New vectors, which are partly characterized, we would like to test their effectiveness in vitro with animal and human tumor cell lines with combination of X-ray. Provided that our result are satisfied, we will go on also with gene therapy of human tumors induced on nude mice or SCID mice with combination of X-ray. We expect improvements of therapeutic retroviral vector with siRNA expression cassette insuring positive or negative regulation of different apoptic pathways.
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