Genetic Circuits in <i>Salmonella typhimurium</i>

Synthetic biology has rapidly progressed over the past decade and is now positioned to impact important problems in health and energy. In the clinical arena, the field has thus far focused primarily on the use of bacteria and bacteriophages to overexpress therapeutic gene products. The next generation of multigene circuits will control the triggering, amplitude, and duration of therapeutic activity <i>in vivo</i>. This will require a host organism that is easy to genetically modify, leverages existing successful circuit designs, and has the potential for use in humans. Here, we show that gene circuits that were originally constructed and tested in <i>Escherichia coli</i> translate to <i>Salmonella typhimurium</i>, a therapeutically relevant microbe with attenuated strains that have exhibited safety in several human clinical trials. These strains are essentially nonvirulent, easy to genetically program, and specifically grow in tumor environments. Developing gene circuits on this platform could enhance our ability to bring sophisticated genetic programming to cancer therapy, setting the stage for a new generation of synthetic biology in clinically relevant microbes

Additional file 1: Figure S1. of FAM3B/PANDER inhibits cell death and increases prostate tumor growth by modulating the expression of Bcl-2 and Bcl-XL cell survival genes

Cell proliferation assays in DU145/FAM3B cells (A) Viable DU145/FAM3B and DU145-control cells were harvested and counted under a light microscope using the trypan blue exclusion method at 48 h intervals during 15 days to determine growth curves. The growth curves shown represent data from three separate experiments. (B) Cell proliferation was measured by labeling cells with bromodeoxyuridine (BrdU) incorporation assay kit according to manufacturer’s protocol. The results are expressed as means of three independent experiments and as relative ratios to BrdU incorporation in DU145-control cells. (TIFF 2263 kb