期刊
ACS SYNTHETIC BIOLOGY
卷 1, 期 10, 页码 458-464出版社
AMER CHEMICAL SOC
DOI: 10.1021/sb300060e
关键词
S. typhimurium; genetic circuits; microfluidics; clinical synthetic biology
资金
- National Institute of General Medical Sciences of the National Institutes of Health [GM069811]
- Department of Defense National Defense Science and Engineering Graduate Fellowship
- National Science Foundation Graduate Research Fellowship
- Misrock Postdoctoral fellowship
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 in vivo. 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 Escherichia coli translate to Salmonella typhimurium, 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.
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