In Vivo Gene Expression Dynamics of Tumor-Targeted Bacteria
Name
Bhatia_In vivo.pdf
Size
3.76 MB
Format
Adobe PDF
Checksum (MD5)
23296e6cacb1adbfefc768f86fe76f42
Author(s)
Danino, Tal
Lo, Justin H.
Prindle, Arthur
Hasty, Jeff
Bhatia, Sangeeta N
Date Issued
September 2012
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
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.
MIT 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
Terms of Use
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.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/sb3000639
