ReviewJournal of thrombosis and haemostasis : JTH2023
Cellular stress and coagulation factor production: when more is not necessarily better.
Review in Journal of thrombosis and haemostasis : JTH, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 17 citations in OpenAlex.
- Defining the safety and efficacy of liver-directed AAV gene therapy using a human liver tissue-equivalent platform.Molecular therapy. Advances · 2026Article
- An ER stress-responsive RNA rheostat for programmable gene and mRNA therapies.Cell chemical biology · 2026Article
- Mechanically Regulated Nanozymes for Remote Metabolic Reprogramming and Precise Cancer Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- Phase 1 pilot study for hemophilia-A: AAV8 vector with prophylactic tacrolimus-glucocorticoid achieves therapeutic FVIII activity.Signal transduction and targeted therapy · 2026Article
- Ranibizumab on optic disc perfusion in central retinal vein occlusion.International journal of ophthalmology · 2026Article
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- Exploring gene editing as a potential therapeutic strategy for hemophilia.Frontiers in bioengineering and biotechnology · 2026Review
- 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
- Cell-Based Small-Molecule Screening Identifying Proteostasis Regulators Enhancing Factor VIII Missense Mutant Secretion.Biomolecules · 2025Article
- Lentiviral Gene Therapy with CD34+ Hematopoietic Cells for Hemophilia A.The New England journal of medicine · 2025Article
- CRISPR and gene editing technologies for bleeding disorders.Therapeutic advances in hematology · 2025Review
- Roctavian gene therapy for hemophilia A.Blood advances · 2024Review
- Adeno-associated virus and hepatocytes: frenemies?Blood advances · 2024Article
- A novel risk stratification approach and molecular subgroup characterization based on coagulation related genes in colon adenocarcinoma.Cancer cell international · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Remarkably, it has been 40 years since the isolation of the 2 genes involved in hemophilia A (HA) and hemophilia B (HB), encoding clotting factor (F) VIII (FVIII) and FIX, respectively. Over the years, these advances led to the development of purified recombinant protein factors that are free of contaminating viruses from human pooled plasma for hemophilia treatments, reducing the morbidity and mortality previously associated with human plasma-derived clotting factors. These discoveries also paved the way for modified factors that have increased plasma half-lives. Importantly, more recent advances have led to the development and Food and Drug Administration approval of a hepatocyte-targeted, adeno-associated viral vector-mediated gene transfer approach for HA and HB. However, major concerns regarding the durability and safety of HA gene therapy remain to be resolved. Compared with FIX, FVIII is a much larger protein that is prone to misfolding and aggregation in the endoplasmic reticulum and is poorly secreted by the mammalian cells. Due to the constraint of the packaging capacity of adeno-associated viral vector, B-domain deleted FVIII rather than the full-length protein is used for HA gene therapy. Like full-length FVIII, B-domain deleted FVIII misfolds and is inefficiently secreted. Its expression in hepatocytes activates the cellular unfolded protein response, which is deleterious for hepatocyte function and survival and has the potential to drive hepatocellular carcinoma. This review is focused on our current understanding of factors limiting FVIII secretion and the potential pathophysiological consequences upon expression in hepatocytes.
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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.