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In Vivo Gene Expression Dynamics of Tumor-Targeted Bacteria

Author(s)
Danino, Tal; Lo, Justin H.; Prindle, Arthur; Hasty, Jeff; Bhatia, Sangeeta N
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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.

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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.
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Abstract
The engineering of bacteria to controllably deliver therapeutics is an attractive application for synthetic biology. While most synthetic gene networks have been explored within microbes, there is a need for further characterization of in vivo circuit behavior in the context of applications where the host microbes are actively being investigated for efficacy and safety, such as tumor drug delivery. One major hurdle is that culture-based selective pressures are absent in vivo, leading to strain-dependent instability of plasmid-based networks over time. Here, we experimentally characterize the dynamics of in vivo plasmid instability using attenuated strains of S. typhimurium and real-time monitoring of luminescent reporters. Computational modeling described the effects of growth rate and dosage on live-imaging signals generated by internal bacterial populations. This understanding will allow us to harness the transient nature of plasmid-based networks to create tunable temporal release profiles that reduce dosage requirements and increase the safety of bacterial therapies.
Date issued
2012-09
URI
http://hdl.handle.net/1721.1/75323
Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Koch Institute for Integrative Cancer Research at MIT
Journal
ACS Synthetic Biology
Publisher
American Chemical Society (ACS)
Citation
Danino, Tal et al. “In Vivo Gene Expression Dynamics of Tumor-Targeted Bacteria.” ACS Synthetic Biology 1.10 (2012): 465–470. Copyright © 2012 American Chemical Society
Version: Final published version
ISSN
2161-5063

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