ArticleNature communications2024
Pre-clinical evaluation of an enhanced-function factor VIII variant for durable hemophilia A gene therapy in male mice.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed.
- Characterization of a mouse model to study mechanisms of hemophilia A pain.Blood advances · 2026Article
- Article
- Characterization of a factor VIII/immunoglobulin heavy chain μ double-knockout mouse model of hemophilia A for long-term exposure to factor VIII proteins.Research and practice in thrombosis and haemostasis · 2026Article
- The Epigenetic Angle in the Precision Medicine Era for Blood Disorder Advancements.Sub-cellular biochemistry · 2026Review
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- Deconstructing gene therapy in hemophilia for the clinician.Hematology. American Society of Hematology. Education Program · 2025Review
- Factor IXa and factor X influence factor VIIIa stability and inactivation mechanisms in vitro and in vivo.Blood · 2025Article
- Use of CD19-targeted immune modulation to eradicate AAV-neutralizing antibodies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- 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
- 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
- Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- Review
- Roctavian gene therapy for hemophilia A.Blood advances · 2024Review
Corrections and comments
- Update of
Authors and funding
5 authors.
Funding
Abstract
Durable factor VIII expression that normalizes hemostasis is an unrealized goal of hemophilia A adeno-associated virus-mediated gene therapy. Trials with initially normal factor VIII activity observed unexplained year-over-year declines in expression while others reported low-level, stable expression inadequate to restore normal hemostasis. Here we demonstrate that male mice recapitulate expression-level-dependent loss of factor VIII levels due to declines in vector copy number. We show that an enhanced function factor VIII variant (factor VIII-R336Q/R562Q), resistant to activated protein C-mediated inactivation, normalizes hemostasis at below-normal expression without evidence of prothrombotic risk in male hemophilia A mice. These data support that factor VIII-R336Q/R562Q may restore normal factor VIII function at low levels of expression to permit durability using low vector doses to minimize dose-dependent adeno-associated virus toxicities. This work informs the mechanism of factor VIII durability after gene transfer and supports that factor VIII-R336Q/R562Q may safely overcome current hemophilia A gene therapy limitations.
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.