Evidence map›Paper›PMID 39920119›Full record

ArticleNature communications2025

A synthetic chronogenetic gene circuit for programmed circadian drug delivery.

Lara Pferdehirt, Anna R Damato, Kristin L Lenz, Maria F Gonzalez-Aponte, Daniel Palmer, Qing-Jun Meng, Erik D Herzog, Farshid Guilak

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Programmable chronogenetic gene circuits for self-regulated circadian delivery of biologic drugs.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  9. Review
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

8 authors.

Lara PferdehirtDepartment of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1968-3636
Anna R DamatoDepartment of Biology, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-3283-3958
Kristin L LenzDepartment of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Maria F Gonzalez-AponteDepartment of Biology, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-8139-312X
Daniel PalmerDepartment of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Qing-Jun MengWellcome Centre for Cell Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-9426-8336
Erik D HerzogDepartment of Biology, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7209-5174
Farshid GuilakDepartment of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, USA. guilak@wustl.edu.ORCID http://orcid.org/0000-0001-7380-0330

Funding

VISCOELASTIC PROPERTIES OF NORMAL AND OA CHONDRONSR01AG015768 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 1998 to 2022
$7.7M
Washington University Rheumatic DiseasesResearch Resource-based CenterP30AR073752 · NIAMS · WASHINGTON UNIVERSITY · PI Alfred Hyoungju Kim · 2018 to 2026
$7.6M
Resource Based Center for Musculoskeletal Biology and Medicine (Overall Application)P30AR074992 · NIAMS · WASHINGTON UNIVERSITY · PI MATTHEW J SILVA · 2019 to 2026
$6.8M
Genetically-engineered stem cells for self-regulating arthritis therapyR01AR080902 · NIAMS · WASHINGTON UNIVERSITY · PI Farshid Guilak, Christine T. Pham · 2022 to 2026
$3.7M
OBESITY, BIOMECHANICS, AND INFLAMMATION IN OSTEOARTHRITISR01AG046927 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 2013 to 2023
$3.2M
Neuroscience Training Program at Washington UniversityT32NS121881 · NINDS · WASHINGTON UNIVERSITY · PI Martha W Bagnall, Daniel Kerschensteiner · 2021 to 2026
$3.1M
Deconstructing Cartilage Mechanotransduction by Piezo ChannelsR01AR072999 · NIAMS · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 2020 to 2024
$2.9M
Collaborative Research: Inferring Dynamic Topology to Decode and Control Spatiotemporal Structures in Complex NetworksR01GM131403 · NIGMS · WASHINGTON UNIVERSITY · PI LI, JR-SHIN · 2018 to 2021
$1.6M
The Role of Fat in OsteoarthritisR00AR078949 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLINS, KELSEY HELEN-MARIE · 2023 to 2025
$715k
The Role of Fat in OsteoarthritisK99AR078949 · NIAMS · WASHINGTON UNIVERSITY · PI COLLINS, KELSEY HELEN-MARIE · 2022 to 2023
$98k
Characterization of circadian rhythms in Glioblastoma multiforme and investigation of chronotherapy as a novel therapy to prolong patient survivalF31CA250161 · NCI · WASHINGTON UNIVERSITY · PI DAMATO, ANNA · 2020 to 2022
$82k
NCI NIH HHS F31 CA250161NIAMS NIH HHS K99 AR078949NIAMS NIH HHS P30 AR073752NIAMS NIH HHS P30 AR074992NIAMS NIH HHS R00 AR078949NIAMS NIH HHS R01 AR072999NIAMS NIH HHS R01 AR080902NIA NIH HHS R01 AG015768NIA NIH HHS R01 AG046927NIGMS NIH HHS R01 GM131403NINDS NIH HHS T32 NS121881U.S. Department of Health & Human Services | National Institutes of Health (NIH) AG15768
6 · The paper itself

Abstract

Circadian medicine, the delivery of therapeutic interventions based on an individual's daily rhythms, has shown improved efficacy and reduced side-effects for various treatments. Rheumatoid arthritis and other inflammatory diseases are characterized by diurnal changes in cytokines, leading to inflammatory flares, with peak disease activity in the early morning. Using a combination of synthetic biology and tissue engineering, we developed circadian-based gene circuits, termed "chronogenetics", that express a prescribed transgene downstream of the core clock gene promoter, Period2 (Per2). Gene circuits were transduced into induced pluripotent stem cells that were tissue-engineered into cartilage constructs. Our anti-inflammatory chronogenetic constructs produced therapeutic concentrations of interleukin-1 receptor antagonist in vitro. Once implanted in vivo, the constructs expressed circadian rhythms and entrained to daily light cycles, producing daily increases in biologic drug at the peak of Per2 expression. This approach represents the development of a cell-based chronogenetic therapy for various applications in circadian medicine.

Indexed as

Circadian RhythmDrug Delivery SystemsGene Regulatory NetworksPeriod Circadian ProteinsAnimalsHumansInduced Pluripotent Stem CellsInterleukin 1 Receptor Antagonist ProteinMicePromoter Regions, GeneticSynthetic BiologyTissue EngineeringInterleukin 1 Receptor Antagonist ProteinPER2 protein, humanPeriod Circadian Proteins

Identifiers

PMID39920119
PMCPMC11806060

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.