ArticleBlood2022
Suppression of fibrin(ogen)-driven pathologies in disease models through controlled knockdown by lipid nanoparticle delivery of siRNA.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- Plasmin-mediated fibrinolysis is required for hematopoietic recovery after 5-FU-induced myeloablation.Blood advances · 2026Article
- The fibrinogen αC region promotes arterial thrombosis in the context of hypofibrinogenemia.Blood · 2026Article
- Article
- Depletion of Fibrinogen Suppresses Growth of Primary Tumors and Metastasis of Pancreatic Ductal Adenocarcinoma.Gastroenterology · 2026Article
- Preclinical safety and bleeding evaluation in swine for a small interfering RNA-lipid nanoparticle that prevents excess fibrinogen synthesis.Journal of thrombosis and haemostasis : JTH · 2026Article
- Racing toward a common biology of venous thromboembolism prophylaxis: the small interfering RNA fibrinogen knockdown strategy.Journal of thrombosis and haemostasis : JTH · 2026Article
- Role of Clot Formation and Plasminogen Activation in Lower Urinary Tract Pathologies.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Targeting autophagy and plasminogen activator inhibitor-1 increases survival and remodels the tumor microenvironment in glioblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Fibrinogen levels and bleeding risk in adult extracorporeal cardiopulmonary resuscitation: multicenter observational study subanalysis.Research and practice in thrombosis and haemostasis · 2025Article
- TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury.Acta neuropathologica · 2024Article
- Regulation of hepatic inclusions and fibrinogen biogenesis by SEL1L-HRD1 ERAD.Nature communications · 2024Article
- Novel Challenges and Opportunities for Anesthesia and Perioperative Care in Microvascular Flap Surgery: A Narrative Review.Clinics and practice · 2024Review
- Regulation of fibrinogen synthesis.Thrombosis research · 2024Review
- RNA therapeutics to control fibrinolysis: review on applications in biology and medicine.Journal of thrombosis and haemostasis : JTH · 2024Review
- siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles.Molecular therapy. Methods & clinical development · 2024Article
- Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A.Science translational medicine · 2024Article
- Prognostic value of the fibrinogen albumin ratio index (FARI) in nasopharyngeal carcinoma patients undergoing radiotherapy.Scientific reports · 2023Article
- Fibrinogen and fibrin: synthesis, structure, and function in health and disease.Journal of thrombosis and haemostasis : JTH · 2023Review
- Association between higher systemic immune inflammation index (SII) and deep vein thrombosis (DVT) in patients with aneurysmal subarachnoid hemorrhage (aSAH) after endovascular treatment.Neurosurgical review · 2023Article
- Novel genetic regulators of fibrinogen synthesis identified by an in vitro experimental platform.Journal of thrombosis and haemostasis : JTH · 2023Article
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Fibrinogen plays a pathologic role in multiple diseases. It contributes to thrombosis and modifies inflammatory and immune responses, supported by studies in mice expressing fibrinogen variants with altered function or with a germline fibrinogen deficiency. However, therapeutic strategies to safely and effectively tailor plasma fibrinogen concentration are lacking. Here, we developed a strategy to tune fibrinogen expression by administering lipid nanoparticle (LNP)-encapsulated small interfering RNA (siRNA) targeting the fibrinogen α chain (siFga). Three distinct LNP-siFga reagents reduced both hepatic Fga messenger RNA and fibrinogen levels in platelets and plasma, with plasma levels decreased to 42%, 16%, and 4% of normal within 1 week of administration. Using the most potent siFga, circulating fibrinogen was controllably decreased to 32%, 14%, and 5% of baseline with 0.5, 1.0, and 2.0 mg/kg doses, respectively. Whole blood from mice treated with siFga formed clots with significantly decreased clot strength ex vivo, but siFga treatment did not compromise hemostasis following saphenous vein puncture or tail transection. In an endotoxemia model, siFga suppressed the acute phase response and decreased plasma fibrinogen, D-dimer, and proinflammatory cytokine levels. In a sterile peritonitis model, siFga restored normal macrophage migration in plasminogen-deficient mice. Finally, treatment of mice with siFga decreased the metastatic potential of tumor cells in a manner comparable to that observed in fibrinogen-deficient mice. The results indicate that siFga causes robust and controllable depletion of fibrinogen and provides the proof-of-concept that this strategy can modulate the pleiotropic effects of fibrinogen in relevant disease models.
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Registered trials
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.