Evidence map›Paper›PMID 26019220›Full record

ArticleScience translational medicine2015

Programmable probiotics for detection of cancer in urine.

Tal Danino, Arthur Prindle, Gabriel A Kwong, Matthew Skalak, Howard Li, Kaitlin Allen, Jeff Hasty, Sangeeta N Bhatia

Abstract read
In one paragraph

Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

182 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Toward development of soil-derivedBiodesign research · 2026
    Article
  9. Review
  10. Article
  11. Review
  12. Bacteria as living biosensors for DNA.Nature reviews bioengineering · 2026
    Article
  13. The renaissance ofFrontiers in immunology · 2026
    Review
  14. Re-evaluating the role ofmicroPublication biology · 2026
    Article
  15. Review
  16. Current and emerging approaches to manage chronic inflammatory gut disorders.Frontiers in cellular and infection microbiology · 2026
    Review
  17. Review
  18. Article
  19. Review
  20. Review

122 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Tal DaninoInstitute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Arthur PrindleDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Gabriel A KwongInstitute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Matthew SkalakInstitute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Howard LiDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Kaitlin AllenInstitute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Jeff HastyDepartment 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.
Sangeeta N BhatiaInstitute 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.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
Engineered Gene Circuits for Basic Science and BiotechnologyR01GM069811 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, TSIMRING, LEV S · 2004 to 2025
$13.6M
NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051NIEHS NIH HHS P30 ES002109NIEHS NIH HHS P30-ES002109NIGMS NIH HHS P50 GM085764NIGMS NIH HHS R01 GM069811NIGMS NIH HHS R01GM69811
6 · The paper itself

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.

Indexed as

Administration, OralAnimalsbeta-GalactosidaseCell Line, TumorDisease Models, AnimalEarly Detection of CancerHumansLiver NeoplasmsMice, NudeNeoplasmsPlasmidsProbioticsSensitivity and SpecificityTime Factorsbeta-Galactosidase

Identifiers

PMID26019220
PMCPMC4511399

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.