ArticleCell stem cell2023
An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.
Open access · greenAbstract read
In one paragraph
Article in Cell stem cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
5.0field-weighted citation impact, top 3% of its field
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.
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.
Who cites it
46 citing papers in PubMed, 64 citations in OpenAlex.
- Immunoengineering External Field Responsive Biomaterials for Tissue Repair and Regeneration.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Enhancer-directed gene delivery for digit regeneration based on conserved epidermal factors.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Signal control during tissue regeneration in adult animals.Nature reviews. Molecular cell biology · 2026Review
- Enhancer-based gene therapy: a new path for precision medicine.Hereditas · 2026Review
- Past, Present and Future of Regenerative Gene Therapy for Ischemic Heart Failure.Journal of cardiovascular translational research · 2026Review
- Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026Review
- The regulatory code of injury-responsive enhancers enables precision cell-state targeting in the CNS.Nature neuroscience · 2026Article
- Single-cell multi-omics data reveal heterogeneity in liver tissue microenvironment induced by hypertension.Molecular therapy. Nucleic acids · 2025Article
- MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis.Genes & development · 2025Article
- Targeting the Hippo Pathway for Cardiac Regeneration.Physiology (Bethesda, Md.) · 2025Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- A threshold level of JNK activates damage-responsive enhancers via JAK/STAT to promote tissue regeneration.Development (Cambridge, England) · 2025Article
- A subset of transposable elements as mechano-response enhancer elements in controlling human embryonic stem cell fate.Nature cell biology · 2025Article
- Dynamic cell fate plasticity and tissue reintegration drive functional adult synovial joint regeneration after complete resection.Nature communications · 2025Article
- Rewiring cell identity and metabolism to drive cardiomyocyte proliferation.Cell regeneration (London, England) · 2025Review
- A mesothelial differentiation gateway drives fibrosis.Nature communications · 2025Article
- Article
- Cardiomyocyte-specific LARP6 overexpression prevents angiotensin II-induced myocardial dysfunction and interstitial fibrosis.American journal of physiology. Heart and circulatory physiology · 2025Article
- Article
Corrections and comments
- Commented on by
Authors and funding
31 authors at 9 institutions in 2 countries.
Ruorong YanDuke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA.
Valentina CigliolaDuke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA.
Kelsey A OonkDuke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA.
Zachary PetroverDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Sophia DeLucaDepartment of Cell Biology, Duke University Medical School, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
David W WolfsonDuke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.
Andrew VeksteinDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Michelle A MendiolaDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Garth DevlinDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Muath BishawiDepartment of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
Matthew P GemberlingDepartment of Biomedical Engineering, Duke University, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.
Tanvi SinhaCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Michelle A SargentDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Allen J YorkDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Avraham ShakkedDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Paige DeBenedittisDepartment of Medicine, Duke University Medical Center, Durham, NC, USA.
David C WendellDuke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Durham, NC, USA.
Jianhong OuDuke Regeneration Center, Duke University, Durham, NC, USA.
Junsu KangDepartment of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Joseph A GoldmanDepartment of Biological Chemistry and Pharmacology, Ohio State University, Columbus, OH, USA.
Gurpreet S BahtDuke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA.
Ravi KarraDepartment of Medicine, Duke University Medical Center, Durham, NC, USA.
Adam R WilliamsDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Dawn E BowlesDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Aravind AsokanDuke Regeneration Center, Duke University, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.
Eldad TzahorDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Charles A GersbachDuke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA.
Jeffery D MolkentinDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Nenad BursacDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Brian L BlackCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Kenneth D PossDuke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA. Electronic address: ken.poss@duke.edu.
Duke University · USApplied Genetic Technologies (United States) · USDuke Medical Center · USWeizmann Institute of Science · ILCincinnati Children's Hospital Medical Center · USUniversity of California, San Francisco · USThe Ohio State University · USUniversity of Cincinnati · USUniversity of Wisconsin–Madison · US
Funding
Resource Core 3 - Metabolomics CoreP30AG028716 · NIA · DUKE UNIVERSITY · PI CATHLEEN S COLON-EMERIC, Susan Nicole Hastings · 2006 to 2026
$24.6MThe Duke FUNCTION Center: Pioneering the comprehensive identification of combinatorial noncoding causes of diseaseRM1HG011123 · NHGRI · DUKE UNIVERSITY · PI GREGORY E CRAWFORD, Raluca Gordan · 2020 to 2026
$21.9MProject 3: Control of cardiac transcription by MEF2 and myocardinP01HL146366 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BRUNEAU, BENOIT GAETAN · 2019 to 2023
$13.7MHigh-Throughput Functional Annotation of Gene Regulatory Elements and Variants Critical to Complex Cellular PhenotypesUM1HG012053 · NHGRI · DUKE UNIVERSITY · PI GREGORY E CRAWFORD, Charles A. Gersbach · 2021 to 2026
$10.7MIntegrated Cellular and Tissue Engineering for Ischemic Heart DiseaseU01HL134764 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BURSAC, NENAD, KAMP, TIMOTHY J. · 2016 to 2022
$7.7MLeveraging zebrafish models to dissect and enhance heart regenerationR35HL150713 · NHLBI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI KENNETH D POSS · 2020 to 2026
$6.9MIdentification and application of regulatory elements for heart regenerationR01HL136182 · NHLBI · DUKE UNIVERSITY · PI BLACK, BRIAN L, POSS, KENNETH D · 2017 to 2020
$3.1MDissecting injury-responsive gene expression during zebrafish heart regenerationR01HL151522 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Junsu Kang · 2021 to 2026
$2.6MUniversity Training Program in Biomolecular and Tissue EngineeringT32GM144291 · NIGMS · DUKE UNIVERSITY · PI Charles A. Gersbach, Tatiana Segura · 2022 to 2026
$2.6MMyovascular Mechanisms of Cardiac Growth and RegenerationR01HL157277 · NHLBI · DUKE UNIVERSITY · PI RAVI KARRA · 2022 to 2026
$2.6MEngineering Human Heart Tissues with Polyploid CardiomyocytesR01HL164013 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD · 2022 to 2025
$2.2MEngineering of Human Excitable Tissues from Unexcitable CellsR01HL126524 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD · 2016 to 2019
$1.9MAmerican Heart Association-American Stroke Association 16SDG30020001American Heart Association-American Stroke Association 17SDG33660922NHGRI NIH HHS RM1 HG011123NHGRI NIH HHS UM1 HG012053NHLBI NIH HHS F31 HL162460NHLBI NIH HHS P01 HL146366NHLBI NIH HHS R01 HL126524NHLBI NIH HHS R01 HL136182NHLBI NIH HHS R01 HL151522NHLBI NIH HHS R01 HL157277NHLBI NIH HHS R01 HL164013NHLBI NIH HHS R35 HL150713NHLBI NIH HHS U01 HL134764NIAID NIH HHS U01 AI146356NIA NIH HHS P30 AG028716NIA NIH HHS R21 AG067245NIDA NIH HHS R33 DA041878NIDDK NIH HHS R01 DK119621NIGMS NIH HHS T32 GM144291
Abstract
The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) isolated from zebrafish can direct targeted, injury-associated gene expression from viral DNA vectors delivered systemically in small and large adult mammalian species. When employed in combination with CRISPR-based epigenome editing tools in mice, zebrafish TREEs stimulated or repressed the expression of endogenous genes after ischemic myocardial infarction. Intravenously delivered recombinant AAV vectors designed with a TREE to direct a constitutively active YAP factor boosted indicators of cardiac regeneration in mice and improved the function of the injured heart. Our findings establish the application of contextual enhancer elements as a potential therapeutic platform for spatiotemporally controlled tissue regeneration in mammals.
Indexed as
Enhancer Elements, GeneticGenetic TherapyHeartMyocardial InfarctionMyocytes, CardiacRegenerationAnimalsCell ProliferationMiceZebrafishcardiomyocyte proliferationenhancersgene therapyheart regenerationmousepigtissue regenerationYAPzebrafish
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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.