ArticleJournal of thrombosis and haemostasis : JTH2014
In vivo enrichment of genetically manipulated platelets corrects the murine hemophilic phenotype and induces immune tolerance even using a low multiplicity of infection.
Article in Journal of thrombosis and haemostasis : JTH, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 36 citations in OpenAlex.
- FVIII-containing platelets modulate immune responses and attenuate inhibitor development in hemophilia A mice.Haematologica · 2026Article
- Impact of antiplatelet therapy on the hemostatic efficacy of platelet-targeted FVIII gene therapy in hemophilia A mice.Blood advances · 2026Article
- The T follicular helper/T follicular helper regulatory pathway in FVIII immune responses in mice.Blood · 2025Article
- Evaluating clinically translatable conditioning for platelet gene therapy in murine hemophilia A with inhibitors.Journal of thrombosis and haemostasis : JTH · 2024Article
- Platelet-targeted gene therapy induces immune tolerance in hemophilia and beyond.Journal of thrombosis and haemostasis : JTH · 2024Review
- Pre-existing anti-factor VIII immunity alters therapeutic platelet-targeted factor VIII engraftment following busulfan conditioning through cytotoxic CD8 T cells.Journal of thrombosis and haemostasis : JTH · 2023Article
- Targeting transmembrane-domain-less MOG expression to platelets prevents disease development in experimental autoimmune encephalomyelitis.Frontiers in immunology · 2022Article
- Thromboelastometry assessment of hemostatic properties in various murine models with coagulopathy and the effect of factor VIII therapeutics.Journal of thrombosis and haemostasis : JTH · 2021Article
- Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.Blood advances · 2021Article
- Platelet gene therapy induces robust immune tolerance even in a primed model via peripheral clonal deletion of antigen-specific T cells.Molecular therapy. Nucleic acids · 2021Article
- Platelet-inspired therapeutics: current status, limitations, clinical implications, and future potential.Drug delivery and translational research · 2021Review
- In vivo enrichment of genetically manipulated platelets for murine hemophilia B gene therapy.Journal of cellular physiology · 2021Article
- Unexpected enhancement of FVIII immunogenicity by endothelial expression in lentivirus-transduced and transgenic mice.Blood advances · 2020Article
- The severe spontaneous bleeding phenotype in a novel hemophilia A rat model is rescued by platelet FVIII expression.Blood advances · 2020Article
- Escape or Fight: Inhibitors in Hemophilia A.Frontiers in immunology · 2020Review
- Platelet-Targeted FVIII Gene Therapy Restores Hemostasis and Induces Immune Tolerance for Hemophilia A.Frontiers in immunology · 2020Review
- Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.Current stem cell reports · 2019Article
- Nongenotoxic antibody-drug conjugate conditioning enables safe and effective platelet gene therapy of hemophilia A mice.Blood advances · 2019Article
- The impact of GPIbα on platelet-targeted FVIII gene therapy in hemophilia A mice with pre-existing anti-FVIII immunity.Journal of thrombosis and haemostasis : JTH · 2019Article
- Platelet-Targeted Gene Therapy for Hemophilia.Molecular therapy. Methods & clinical development · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundOur previous studies have demonstrated that platelet-specific gene delivery to hematopoietic stem cells can induce sustained therapeutic levels of platelet factor VIII (FVIII) expression in mice with hemophilia A.
objectiveIn this study, we aimed to enhance platelet FVIII expression while minimizing potential toxicities.
methodsA novel lentiviral vector (LV), which harbors dual genes, the FVIII gene driven by the αIIb promoter (2bF8) and a drug-resistance gene, the MGMT(P140K) cassette, was constructed. Platelet FVIII expression in mice with hemophilia A was introduced by transduction of hematopoietic stem cells and transplantation. The recipients were treated with O(6)-benzylguanine followed by 1,3-bis-2 chloroethyl-1-nitrosourea monthly three or four times. Animals were analyzed by using polymerase chain reaction (PCR), quantitative PCR, FVIII:C assays, and inhibitor assays. Phenotypic correction was assessed by tail clipping tests and rotational thromboelastometry analysis.
resultsEven using a low multiplicity of infection of 1 and a non-myeloablative conditioning regimen, after in vivo selection, the levels of platelet FVIII expression in recipients increased to 4.33 ± 5.48 mU per 10(8) platelets (n = 16), which were 19.7-fold higher than the levels obtained from the recipients before treatment. Quantitative PCR results confirmed that 2bF8/MGMT-LV-transduced cells were effectively enriched after drug-selective treatment. Fifteen of 16 treated animals survived tail clipping. Blood loss and whole blood clotting time were normalized in the treated recipients. Notably, no anti-FVIII antibodies were detected in the treated animals even after recombinant human B-domain deleted FVIII challenge.
conclusionwe have established an effective in vivo selective system that allows us to enrich 2bF8LV-transduced cells, enhancing platelet FVIII expression while reducing the potential toxicities associated with platelet gene therapy.
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.