Evidence map›Paper›PMID 39266721›Full record

ArticleNature chemical biology2025

Customizable gene sensing and response without altering endogenous coding sequences.

Fabio Caliendo, Elvira Vitu, Junmin Wang, Shuo-Hsiu Kuo, Hayden Sandt, Casper Nørskov Enghuus, Jesse Tordoff, Neslly Estrada, James J Collins, Ron Weiss

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  5. 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

10 authors.

Fabio Caliendo *Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-5676-6000
Elvira Vitu *Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Junmin WangBioinformatics Graduate Program, Boston University, Boston, MA, USA.
Shuo-Hsiu KuoSynthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0009-0004-2071-7356
Hayden SandtDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Casper Nørskov EnghuusDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jesse TordoffDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Neslly EstradaDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
James J CollinsDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-5560-8246
Ron WeissDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. rweiss@mit.edu.ORCID 0000-0003-0396-2443

Funding

Molecular Circuits in the Hematopoietic Stem Cell NicheRC2DK120535 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2020 to 2024
$8.2M
Genetically Programmed Pancreatic Organoids with Self-Adaptive Multi-Lineage Population ControlR01HD105947 · NICHD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WEISS, RON · 2021 to 2025
$3.2M
Selection of the B Cell Repertoire in SenescenceR01AG025256 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI RILEY, RICHARD L · 2004 to 2016
$3.2M
National Science Foundation (NSF) CNS-1446474United States Department of Defense | Defense Advanced Research Projects Agency (DARPA) HR0011-20-2-0005United States Department of Defense | Defense Advanced Research Projects Agency (DARPA) W911NF19C0008United States Department of Defense | United States Army | U.S. Army Research, Development and Engineering Command | Army Research Office (ARO) W911NF-17-3-003U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 5R01HD105947-03U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 5-R01-EB025256-04U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 5-R01-EB030946-04U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) 5RC2DK120535
6 · The paper itself

Abstract

Synthetic biology aims to modify cellular behaviors by implementing genetic circuits that respond to changes in cell state. Integrating genetic biosensors into endogenous gene coding sequences using clustered regularly interspaced short palindromic repeats and Cas9 enables interrogation of gene expression dynamics in the appropriate chromosomal context. However, embedding a biosensor into a gene coding sequence may unpredictably alter endogenous gene regulation. To address this challenge, we developed an approach to integrate genetic biosensors into endogenous genes without modifying their coding sequence by inserting into their terminator region single-guide RNAs that activate downstream circuits. Sensor dosage responses can be fine-tuned and predicted through a mathematical model. We engineered a cell stress sensor and actuator in CHO-K1 cells that conditionally activates antiapoptotic protein BCL-2 through a downstream circuit, thereby increasing cell survival under stress conditions. Our gene sensor and actuator platform has potential use for a wide range of applications that include biomanufacturing, cell fate control and cell-based therapeutics.

Indexed as

Biosensing TechniquesAnimalsCHO CellsCricetulusCRISPR-Cas SystemsGene Expression RegulationOpen Reading FramesProto-Oncogene Proteins c-bcl-2RNA, Guide, CRISPR-Cas SystemsSynthetic BiologyProto-Oncogene Proteins c-bcl-2RNA, Guide, CRISPR-Cas Systems

Identifiers

What OpenQuestion holds

Textmetadata
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.