Genetic Circuits in Salmonella typhimurium
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 gene...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society (ACS)
2012
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| Online Access: | http://hdl.handle.net/1721.1/75313 https://orcid.org/0000-0002-1293-2097 https://orcid.org/0000-0001-7302-4394 |
| Summary: | 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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