Format

Send to

Choose Destination
Sci Transl Med. 2015 May 27;7(289):289ra84. doi: 10.1126/scitranslmed.aaa3519.

Programmable probiotics for detection of cancer in urine.

Author information

1
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
2
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
3
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. BioCircuits Institute, University of California, San Diego, La Jolla, CA 92093, USA. Molecular Biology Section, Division of Biological Science, University of California, San Diego, La Jolla, CA 92093, USA.
4
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Electrical Engineering and Computer Science and David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. sbhatia@mit.edu.

Abstract

Rapid advances in the forward engineering of genetic circuitry in living cells has positioned synthetic biology as a potential means to solve numerous biomedical problems, including disease diagnosis and therapy. One challenge in exploiting synthetic biology for translational applications is to engineer microbes that are well tolerated by patients and seamlessly integrate with existing clinical methods. We use the safe and widely used probiotic Escherichia coli Nissle 1917 to develop an orally administered diagnostic that can noninvasively indicate the presence of liver metastasis by producing easily detectable signals in urine. Our microbial diagnostic generated a high-contrast urine signal through selective expansion in liver metastases (10(6)-fold enrichment) and high expression of a lacZ reporter maintained by engineering a stable plasmid system. The lacZ reporter cleaves a substrate to produce a small molecule that can be detected in urine. E. coli Nissle 1917 robustly colonized tumor tissue in rodent models of liver metastasis after oral delivery but did not colonize healthy organs or fibrotic liver tissue. We saw no deleterious health effects on the mice for more than 12 months after oral delivery. Our results demonstrate that probiotics can be programmed to safely and selectively deliver synthetic gene circuits to diseased tissue microenvironments in vivo.

Comment in

PMID:
26019220
PMCID:
PMC4511399
DOI:
10.1126/scitranslmed.aaa3519
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center