ArticleBlood advances2021
Evolutionary insights into coagulation factor IX Padua and other high-specific-activity variants.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 30 citations in OpenAlex.
- Completion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years.Blood advances · 2025Trial
- Article
- Exploring gene editing as a potential therapeutic strategy for hemophilia.Frontiers in bioengineering and biotechnology · 2026Review
- "An integrated multitool analysis contributes elements to interpreting unclassified factor IX missense variants associated with hemophilia B": comment from Lee et al.Journal of thrombosis and haemostasis : JTH · 2025Article
- The Construction of a Molecular Model for the Ternary Protein Complex of Intrinsic Coagulation Pathway Factors Provides Novel Insights for the Pathogenesis of Cross-Reactive Material Positive Coagulation Factor Mutations.International journal of molecular sciences · 2025Article
- Gene therapy for hemophilia - From basic science to first approvals of "one-and-done" therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- AAVrh.10 delivery of novel APOE2-Christchurch variant suppresses amyloid and Tau pathology in Alzheimer's disease mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
- Review
- Adeno-associated virus and hepatocytes: frenemies?Blood advances · 2024Article
- Enhanced procoagulant activity of select hemophilia B causing factor IX variants with emicizumab.Blood · 2024Article
- An RNA aptamer exploits exosite-dependent allostery to achieve specific inhibition of coagulation factor IXa.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Humanization and functional characterization of enhanced coagulation factor IX variants identified through ancestral sequence reconstruction.Journal of thrombosis and haemostasis : JTH · 2024Article
- [Gene therapy of Hemophilia: Recommendations from the German, Austrian, and Swiss Society for Thrombosis and Haemostasis Research (GTH)].Hamostaseologie · 2023Article
- CRISPR-Mediated In Situ Introduction or Integration ofInternational journal of molecular sciences · 2023Article
- SAXS analysis of the intrinsic tenase complex bound to a lipid nanodisc highlights intermolecular contacts between factors VIIIa/IXa.Blood advances · 2022Article
- Gene therapy - are we ready now?Haemophilia : the official journal of the World Federation of Hemophilia · 2022Article
- Coagulation factor IX gene transfer to non-human primates using engineered AAV3 capsid and hepatic optimized expression cassette.Molecular therapy. Methods & clinical development · 2021Article
- Gene Therapy in Hemophilia: Recent Advances.International journal of molecular sciences · 2021Review
- Effect of CpG Depletion of Vector Genome on CD8Frontiers in immunology · 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
7 authors at 2 institutions in 1 country.
Funding
Abstract
The high-specific-activity factor IX (FIX) variant Padua (R338L) is the most promising transgene for hemophilia B (HB) gene therapy. Although R338 is strongly conserved in mammalian evolution, amino acid substitutions at this position are underrepresented in HB databases. We therefore undertook a complete 20 amino acid scan and determined the specific activity of human (h) and canine (c) FIX variants with every amino acid substituted at position 338. Notably, we observe that hFIX-R338L is the most active variant and cFIX-R338L is sevenfold higher than wild-type (WT) cFIX. This is consistent with the previous identification of hFIX-R338L as a cause of a rare X-linked thrombophilia risk factor. Moreover, WT hFIX and cFIX are some of the least active variants. We confirmed the increased specific activity relative to FIX-WT in vivo of a new variant, cFIX-R338I, after gene therapy in an HB dog. Last, we screened 232 pediatric subjects with thromboembolic disease without identifying F9 R338 variants. Together these observations suggest a surprising evolutionary pressure to limit FIX activity with WT FIX rather than maximize FIX activity.
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.