Evidence map›Paper›PMID 34464083›Full record

ArticleACS synthetic biology2021

Synthetic Circuit-Driven Expression of Heterologous Enzymes for Disease Detection.

Jiang He, Lior Nissim, Ava P Soleimany, Adina Binder-Nissim, Heather E Fleming, Timothy K Lu, Sangeeta N Bhatia

Open access · hybridAbstract read
In one paragraph

Article in ACS synthetic biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 38% of its field
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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine.International journal of molecular sciences · 2022
    Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 2 countries.

Jiang HeKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Lior NissimSynthetic Biology Group, Research Laboratory of Electronics, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.ORCID 0000-0001-6495-4741
Ava P SoleimanyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.ORCID 0000-0002-8601-6040
Adina Binder-NissimSynthetic Biology Group, Research Laboratory of Electronics, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Heather E FlemingKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Timothy K LuSynthetic Biology Group, Research Laboratory of Electronics, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.ORCID 0000-0002-3918-8923
Sangeeta N BhatiaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.ORCID 0000-0002-1293-2097
Harvard–MIT Division of Health Sciences and Technology · USMassachusetts Institute of Technology · USBroad Institute · USHebrew University of Jerusalem · ILMicrosoft (United States) · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 1985 to 2020
$25.6M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NIEHS NIH HHS P30 ES002109NIGMS NIH HHS T32 GM008313
6 · The paper itself

Abstract

The integration of nanotechnology and synthetic biology could lay the framework for new classes of engineered biosensors that produce amplified readouts of disease states. As a proof-of-concept demonstration of this vision, here we present an engineered gene circuit that, in response to cancer-associated transcriptional deregulation, expresses heterologous enzyme biomarkers whose activity can be measured by nanoparticle sensors that generate amplified detection readouts. Specifically, we designed an AND-gate gene circuit that integrates the activity of two ovarian cancer-specific synthetic promoters to drive the expression of a heterologous protein output, secreted Tobacco Etch Virus (TEV) protease, exclusively from within tumor cells. Nanoparticle probes were engineered to carry a TEV-specific peptide substrate in order to measure the activity of the circuit-generated enzyme to yield amplified detection signals measurable in the urine or blood. We applied our integrated sense-and-respond system in a mouse model of disseminated ovarian cancer, where we demonstrated measurement of circuit-specific TEV protease activity both

Indexed as

AnimalsBiomarkersBiosensing TechniquesCell Line, TumorEndopeptidasesFemaleFluorescent DyesHumansMiceMice, NudeNanoparticlesNanotechnologyOvarian NeoplasmsPeptidesTransplantation, HeterologousBiomarkersEndopeptidasesFluorescent DyesPeptidesTEV proteaseactivity probesbiomarkerscancernanosensorsnanotechnologyproteasessynthetic biology

Identifiers

PMID34464083
PMCPMC12285725
OpenAlexW3198168808

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.