Evidence map›Paper›PMID 41076269›Full record

ArticleJournal of thrombosis and haemostasis : JTH2026

Preclinical safety and bleeding evaluation in swine for a small interfering RNA-lipid nanoparticle that prevents excess fibrinogen synthesis.

Monica S Seadler, Francesca Ferraresso, Halen M Turner, Laura M Ketelboeter, Youjie Zhang, Katherine Badior, William G Hayssen, Taylor Chen, Amber L Haugen, Massimo F Cau and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

17 authors.

Monica S SeadlerDivision of Trauma, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Versiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Francesca FerraressoVersiti Blood Research Institute, Milwaukee, Wisconsin, USA; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Halen M TurnerDivision of Trauma, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Versiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Laura M KetelboeterVersiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Youjie ZhangVersiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Katherine BadiorVersiti Blood Research Institute, Milwaukee, Wisconsin, USA.
William G HayssenDivision of Trauma, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Versiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Taylor ChenVersiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Amber L HaugenDivision of Trauma, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Versiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Massimo F CauDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Madelaine RobertsonDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Chad SkaerVersiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Muskan BansalVersiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Patrick B MurphyDivision of Trauma, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Marc de MoyaDivision of Trauma, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Mitchell R DyerVersiti Blood Research Institute, Milwaukee, Wisconsin, USA; Division of Vascular Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Christian J KastrupDivision of Trauma, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Versiti Blood Research Institute, Milwaukee, Wisconsin, USA; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada; Departments of Biochemistry, Biomedical Engineering, and Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Electronic address: ckastrup@versiti.org.

Funding

Using novel RNA therapy to understand the role of fibrinogen in thromboinflammation in acute and chronic venous thrombosisK08HL177422 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Mitchell R Dyer · 2025 to 2026
$303k
NHLBI NIH HHS K08 HL177422
6 · The paper itself

Abstract

backgroundFibrinogen levels can drastically increase from inflammation, trauma, or surgery, which increases risk of venous thromboembolism (VTE). We developed small interfering RNA (siFibrinogen) that decreased fibrinogen production and thrombosis in rodent models, which became effective hours after administration and knockdown lasted over a week. Here, we tested whether knockdown of fibrinogen was feasible and safe in a preclinical large animal model. We hypothesized that fibrinogen could be controllably knocked down to levels that still enable hemostasis and avoid limitations of the current standard of care agent, low-molecular-weight heparin (LMWH).

objectivesThis study evaluated the preclinical safety and feasibility of a novel therapy for VTE prophylaxis for complications in trauma and surgical patients.

methodsFemale Yorkshire/cross swine (7-15 kg) were infused with small interfering RNA targeting fibrinogen (siFibrinogen), LMWH, or a vehicle control. Hemostasis was assessed in an established model of hemorrhagic shock. Reversibility was evaluated by administering fibrinogen concentrate.

resultsCirculating fibrinogen concentrations decreased in swine in a dose-dependent manner, lasting over a week from 1 injection of siFibrinogen. Fibrinogen reduction to levels > 0.4 g/L did not impair hemostasis during hemorrhagic shock when compared with LMWH or vehicle control. The effects of siFibrinogen were reversed by the administration of fibrinogen concentrate. No infusion-related reactions or toxicity was observed.

conclusionsiFibrinogen represents a promising novel approach for VTE prophylaxis, avoiding limitations of LMWH. siFibrinogen administered early in patient care could decrease fibrinogen in a sustained and predictable manner to prevent thrombosis while preserving hemostasis.

Indexed as

FibrinogenLipidsNanoparticlesRNAi TherapeuticsRNA, Small InterferingShock, HemorrhagicVenous ThromboembolismAnimalsDisease Models, AnimalFemaleHemorrhageHemostasisHeparin, Low-Molecular-WeightLiposomesSus scrofaSwineFibrinogenHeparin, Low-Molecular-WeightLipid NanoparticlesLipidsLiposomesRNA, Small InterferingfibrinogensiRNAthromboembolismthromboinflammation

Identifiers

PMID41076269
PMCPMC12766900

What OpenQuestion holds

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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.