Retrotransposon Targeting of Tumor Cells
Final rept. 15 Sep 2004-14 Sep 2005
BIOSTAR LLC MCLEAN VA
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Cancer gene therapy might provide highly selective, treatment without systemic toxicity. Cancer gene therapy techniques include oncogene inactivation, tumor suppressor gene replacement, inhibition of angiogenesis, immunopotentiation, molecular chemotherapy, and transfer of drug resistance genes. These treatments have enjoyed only limited success. We propose to use suicide gene therapy transfection of cancer cells with genes that encode enzymes able to activate nontoxic pro-drugs in situ to form cytotoxic products. After insertion of the suicide gene constructs into the cancer cells, we will apply high doses of a relatively non-toxic pro-drug. Intracellular conversion of the pro-drug into the cytotoxic form will result in high concentrations within the cell, and kill the cancer cell. We designed and codon optimized the desired vectors. We constructed a vector to deliver special suicide gene TK into tumor cell lines. The vector with selectable marker gene, promoter and codon optimized suicide genes were transfected into breast cancer cell lines. We examined the expression of the transfected gene in the cell culture by RT-PCR and special colony assay. Adequate levels of expression were not attained in these experiments.
- Medicine and Medical Research