ArticleBlood advances2023
Small interfering RNA-mediated allele-selective silencing of von Willebrand factor in vitro and in vivo.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Novel therapies for von Willebrand disease.Blood advances · 2026Review
- Von Willebrand Factor as a Therapeutic Target in Thrombotic Disorders.Thrombosis and haemostasis · 2026Review
- Hemostasis at the edge between physiology and cancer.Internal and emergency medicine · 2026Review
- HMB-002: a monovalent antibody that elevates circulating VWF and FVIII levels for treatment of von Willebrand disease.Blood advances · 2026Article
- Allele-selective disruption of pathogenic VWF variants in type 2 von Willebrand disease using CRISPR/Cas9.Blood advances · 2026Article
- Allele-selective von Willebrand factor silencing.Research and practice in thrombosis and haemostasis · 2026Article
- Gynecologic and obstetric management of girls and women with von Willebrand disease.Haematologica · 2026Review
- Correction of VWF multimerization in type 2A/IIC von Willebrand disease by exogenous VWF propeptide supplementation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The future of siRNA-mediated approaches to treat von Willebrand disease.Expert review of hematology · 2025Review
- Amelioration of a von Willebrand disease type 2B phenotype in vivo upon treatment with allele-selective siRNAs.Blood advances · 2025Article
- Silencing of the von Willebrand factor gene in proatherothromboticResearch and practice in thrombosis and haemostasis · 2025Article
- Rewriting the script: gene therapy and genome editing for von Willebrand Disease.Frontiers in genome editing · 2025Review
- Prophylaxis in von Willebrand disease with von Willebrand factor concentrate and nonfactor therapies.Research and practice in thrombosis and haemostasis · 2024Article
- von Willebrand disease.Nature reviews. Disease primers · 2024Review
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An imbalance in von Willebrand factor (VWF) may either lead to bleeding (von Willebrand disease, VWD) or thrombosis. Both disorders have shortcomings in the currently available treatments. VWF itself could be a potential therapeutic target because of its role in both bleeding and thrombosis. Inhibiting VWF gene expression through allele-selective silencing of VWF with small interfering RNAs (siRNAs) could be a personalized approach to specifically inhibit mutant VWF in VWD or to normalize increased VWF levels in thrombotic disorders without complete VWF knockdown. Therefore, we investigated a method to allele-selectively silence the VWF gene in mice as a therapeutic strategy. Fourteen candidate siRNAs targeting murine Vwf of either the C57BL/6J (B6) or the 129S1/SvImJ (129S) strain were tested in vitro in cells expressing B6- and 129S-Vwf for inhibitory effect and allele-selective potential. Together with a nonselective siVwf, 2 lead candidate siRNAs, siVwf.B6 and siVwf.129S, were further tested in vivo in B6 and 129S mice. Efficient endothelial siRNA delivery was achieved by siRNA encapsulation into 7C1 oligomeric lipid nanoparticles. Treatment with the nonselective siVwf resulted in dose-dependent inhibition of up to 80% of both lung messenger RNA and plasma VWF protein in both mouse strains. In contrast, the allele-selective siVwf.B6 and siVwf.129S were shown to be effective in and selective solely for their corresponding mouse strain. To conclude, we showed efficient endothelial delivery of siRNAs that are highly effective in allele-selective inhibition of Vwf in mice, which constitutes an in vivo proof of principle of allele-selective VWF silencing as a therapeutic approach.
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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.