Evidence map›Paper›PMID 40143548›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Bispecific receptor decoy proteins block ocular neovascularization via simultaneous blockade of vascular endothelial growth factor A and C.

Paul R Sargunas, Emily Ariail, Raquel Lima E Silva, Akash Patil, Mingliang Zhang, Jikui Shen, Beatriz Silva Lopes, Yuseong Oh, Amelia C McCue, Ranjani Ramasubramanian and 4 more

Abstract read
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In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Bispecific receptor decoys: A new player to a crowded field.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    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

14 authors.

Paul R SargunasDepartment of Chemical and Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Emily AriailTranslational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
Raquel Lima E SilvaDepartment of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Akash PatilDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
Mingliang ZhangDepartment of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Jikui ShenDepartment of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Beatriz Silva LopesDepartment of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21231, USA.
Yuseong OhDepartment of Chemical and Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
Amelia C McCueTranslational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
Ranjani RamasubramanianDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
A Carson StephensonDepartment of Chemical and Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Aleksander S PopelDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Peter A CampochiaroDepartment of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Jamie B SpanglerDepartment of Chemical and Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Institute for NanoBioTechnology, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Department of Materials Science and Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: jamie.spangler@jhu.edu.

Funding

Predictive experiment-based multiscale models of the tumor immune microenvironment and immunotherapy in breast cancerR01CA138264 · NCI · JOHNS HOPKINS UNIVERSITY · PI POPEL, ALEKSANDER S. · 2009 to 2023
$8.1M
Visual Science Training ProgramT32EY007143 · NEI · JOHNS HOPKINS UNIVERSITY · PI Laura Ensign, JEREMY NATHANS · 1995 to 2026
$6.2M
Integrin-binding Peptide for Ocular Neovascularization and Macular Edema: Molecular Mechanism of ActionR01EY028996 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jordan Green · 2019 to 2026
$2.7M
Suprachoroidal nonviral gene transfer of engineered VEGF antagonistsR01EY031097 · NEI · JOHNS HOPKINS UNIVERSITY · PI CAMPOCHIARO, PETER A, GREEN, JORDAN · 2020 to 2023
$2.4M
Design of de novo interleukin mimics for targeted immunotherapyR01CA240339 · NCI · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID · 2019 to 2023
$2.1M
Molecular Engineering of Novel Therapies to Treat Corneal NeovascularizationR21EY033934 · NEI · JOHNS HOPKINS UNIVERSITY · PI SODHI, AKRIT SINGH · 2023 to 2024
$450k
NCI NIH HHS R01 CA138264NCI NIH HHS R01 CA240339NEI NIH HHS R01 EY028996NEI NIH HHS R01 EY031097NEI NIH HHS R21 EY033934NEI NIH HHS T32 EY007143
6 · The paper itself

Abstract

Several debilitating eye diseases that lead to vision loss are driven by ocular neovascularization, which entails abnormal blood vessel growth in the eye. Neovascularization is often induced by the upregulation of vascular endothelial growth factor (VEGF) ligands, which activate angiogenesis through engagement of VEGF receptor (VEGFR) proteins on endothelial cells. Therapeutic interventions that block ocular neovascularization by targeting VEGF ligands, particularly VEGF-A, have revolutionized eye disease treatment. However, a significant population of patients are either non-responders or develop resistance, which can be driven by the upregulation of other VEGF family ligands such as VEGF-C. Here, we engineered two bispecific receptor decoy fusion proteins that incorporate domains of VEGFR-1 and VEGFR-2 for more effective and comprehensive inhibition of VEGF ligands. We demonstrated that our engineered proteins bind all VEGF ligands and can sequester two ligands simultaneously. We further showed that these molecules block VEGF activity to potently inhibit proliferation, migration, and survival of human endothelial cells. Moreover, these receptor decoy proteins significantly reduced ocular neovascularization in two mouse models at doses wherein the current standard-of-care anti-VEGF therapy is ineffective. Collectively, our engineered receptor decoy proteins present a new architecture for VEGF pathway inhibition, offering a promising treatment paradigm for ocular diseases.

Indexed as

Angiogenesis InhibitorsNeovascularization, PathologicRecombinant Fusion ProteinsVascular Endothelial Growth Factor AAnimalsCell MovementCell ProliferationDisease Models, AnimalEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsMiceVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2Angiogenesis InhibitorsRecombinant Fusion ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2angiogenesisanti-angiogenic therapyfusion proteinneovascularizationprotein engineeringreceptor decoy trapvascular endothelial growth factor, VEGFvision loss

Identifiers

PMID40143548
PMCPMC12265965

What OpenQuestion holds

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Registered trials

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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.