Using the Salmonella Typhimurium FNR Protein to Target Therapeutic Gene Expression in Hypoxic Sites in Diseased Tissues

The delivery of drugs to their site of action is a fundamental barrier to the full exploitation of post- genomics in healthcare. For example, one of the most crucial aspects of gene therapy for cancer continues to be targeting of therapeutic gene expression to solid tumours which possess anoxic/hypoxic regions that are difficult to treat conventionally. Thus, we propose to investigate the utility of the anaerobic transcription factor FNR for targeting therapeutic gene expression to hypoxic sites of tumours using S. typhimurium as the delivery vehicle. <P>
We will: construct the necessary strains; use an FNR-regulated reporter/therapeutic gene to monitor gene expression in S. typhimurium during invasion of tumour spheroids; and modify promoter architecture and FNR properties to improve the targeting of therapeutic gene expression.