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...

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Main Authors: Prindle, Arthur, Selimkhanov, Jangir, Danino, Tal, Samayoa, Phillip, Goldber, Anna, Hasty, Jeff, Bhatia, Sangeeta N
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Language:en_US
Published: American Chemical Society (ACS) 2012
Online Access:http://hdl.handle.net/1721.1/75313
https://orcid.org/0000-0002-1293-2097
https://orcid.org/0000-0001-7302-4394
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author Prindle, Arthur
Selimkhanov, Jangir
Danino, Tal
Samayoa, Phillip
Goldber, Anna
Hasty, Jeff
Bhatia, Sangeeta N
author2 Massachusetts Institute of Technology. Institute for Medical Engineering & Science
author_facet Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Prindle, Arthur
Selimkhanov, Jangir
Danino, Tal
Samayoa, Phillip
Goldber, Anna
Hasty, Jeff
Bhatia, Sangeeta N
author_sort Prindle, Arthur
collection MIT
description 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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spelling mit-1721.1/753132022-09-29T19:53:46Z Genetic Circuits in Salmonella typhimurium Prindle, Arthur Selimkhanov, Jangir Danino, Tal Samayoa, Phillip Goldber, Anna Hasty, Jeff Bhatia, Sangeeta N Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Danino, Tal Bhatia, Sangeeta N. 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. National Institutes of Health (U.S.) (Grant GM069811) Misrock Foundation (Postdoctoral Fellowship) 2012-12-10T15:22:00Z 2012-12-10T15:22:00Z 2012-08 2012-07 Article http://purl.org/eprint/type/JournalArticle 2161-5063 http://hdl.handle.net/1721.1/75313 Prindle, Arthur et al. “Genetic Circuits in Salmonella Typhimurium.” ACS Synthetic Biology 1.10 (2012): 458–464. Copyright © 2012 American Chemical Society https://orcid.org/0000-0002-1293-2097 https://orcid.org/0000-0001-7302-4394 en_US http://dx.doi.org/10.1021/sb300060e ACS Synthetic Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) American Chemical Society
spellingShingle Prindle, Arthur
Selimkhanov, Jangir
Danino, Tal
Samayoa, Phillip
Goldber, Anna
Hasty, Jeff
Bhatia, Sangeeta N
Genetic Circuits in Salmonella typhimurium
title Genetic Circuits in Salmonella typhimurium
title_full Genetic Circuits in Salmonella typhimurium
title_fullStr Genetic Circuits in Salmonella typhimurium
title_full_unstemmed Genetic Circuits in Salmonella typhimurium
title_short Genetic Circuits in Salmonella typhimurium
title_sort genetic circuits in salmonella typhimurium
url http://hdl.handle.net/1721.1/75313
https://orcid.org/0000-0002-1293-2097
https://orcid.org/0000-0001-7302-4394
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