ArticleBlood2013
Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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
57 citing papers in PubMed, 83 citations in OpenAlex.
- B cell-activating factor modulates the factor VIII immune response in hemophilia A.The Journal of clinical investigation · 2021Trial
- Advancements in CRISPR-basedFrontiers in genome editing · 2026Review
- Review
- Factor IXa and factor X influence factor VIIIa stability and inactivation mechanisms in vitro and in vivo.Blood · 2025Article
- Transamniotic Delivery of Coagulation Factor VIII mRNA: A Step Toward a Potential Novel Strategy for the Perinatal Management of Hemophilia A.FASEB bioAdvances · 2025Article
- Use of CD19-targeted immune modulation to eradicate AAV-neutralizing antibodies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- RNAi targeting heparin cofactor II promotes hemostasis in a canine model of acquired hemophilia A.Gene therapy · 2025Article
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The deLIVERed promises of gene therapy: Past, present, and future of liver-directed gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Ancient origin of the furin sequence in the wolf F8 gene.Open veterinary journal · 2025Article
- Enhancing hemophilia A gene therapy by strategic F8 deletions in AAV vectors.Blood science (Baltimore, Md.) · 2025Article
- AAV gene therapy in companion dogs with severe hemophilia: Real-world long-term data on immunogenicity, efficacy, and quality of life.Molecular therapy. Methods & clinical development · 2024Article
- Analysis of vector genome integrations in multicentric lymphoma after AAV gene therapy in a severe hemophilia A dog.Molecular therapy. Methods & clinical development · 2023Article
- Cellular stress and coagulation factor production: when more is not necessarily better.Journal of thrombosis and haemostasis : JTH · 2023Review
- Factor VIII mutated with Lys1813Ala within the factor IXa-binding region enhances intrinsic coagulation potential.Blood advances · 2023Article
- Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice.Cellular immunology · 2023Article
- Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice.Blood advances · 2022Article
- Preclinical assessment of an optimized AAV-FVIII vector in mice and non-human primates for the treatment of hemophilia A.Molecular therapy. Methods & clinical development · 2022Article
- Article
- Molecular coevolution of coagulation factor VIII and von Willebrand factor.Blood advances · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant canine B-domain deleted (BDD) factor VIII (FVIII) is predominantly expressed as a single-chain protein and exhibits greater stability after activation compared with human FVIII-BDD. We generated a novel BDD-FVIII variant (FVIII-RH) with an amino acid change at the furin cleavage site within the B domain (position R1645H) that mimics the canine sequence (HHQR vs human RHQR). Compared with human FVIII-BDD, expression of FVIII-RH protein revealed a 2.5-fold increase in the single-chain form. Notably, FVIII-RH exhibited a twofold increase in biological activity compared with FVIII-BDD, likely due to its slower dissociation of the A2-domain upon thrombin activation. Injection of FVIII-RH protein in hemophilia A (HA) mice resulted in more efficacious hemostasis following vascular injury in both the macro- and microcirculation. These findings were successfully translated to adeno-associated viral (AAV)-based liver gene transfer in HA mice. Expression of circulating FVIII-RH was approximately twofold higher compared with AAV-FVIII-BDD-injected mice. Moreover, FVIII-RH exhibits superior procoagulant effects compared with FVIII-BDD following a series of hemostatic challenges. Notably, the immunogenicity of FVIII-RH did not differ from FVIII-BDD. Thus, FVIII-RH is an attractive bioengineered molecule for improving efficacy without increased immunogenicity and may be suitable for both protein- and gene-based strategies for HA.
Indexed as
Identifiers
What OpenQuestion holds
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.