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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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.
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
ACS Synthetic Biology
American Chemical Society (ACS)
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
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