ArticleJournal of thrombosis and haemostasis : JTH2011
Muscle-directed gene therapy for hemophilia B with more efficient and less immunogenic AAV vectors.
Article in Journal of thrombosis and haemostasis : JTH, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- CD8+ T cell activation occurs 24 hours after AAV administration and is driven by muscle promoter specificity.JCI insight · 2026Article
- AAV-DJ is superior to AAV9 for targeting brain and spinal cord, and de-targeting liver across multiple delivery routes in mice.Journal of translational medicine · 2024Article
- Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.Blood advances · 2021Article
- Superior human hepatocyte transduction with adeno-associated virus vector serotype 7.Gene therapy · 2019Article
- Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Multilineage transduction of resident lung cells in vivo by AAV2/8 for α1-antitrypsin gene therapy.Molecular therapy. Methods & clinical development · 2016Article
- Treatment of hypophosphatasia by muscle-directed expression of bone-targeted alkaline phosphatase via self-complementary AAV8 vector.Molecular therapy. Methods & clinical development · 2016Article
- Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies.Molecular therapy. Methods & clinical development · 2016Review
- The potential of adeno-associated viral vectors for gene delivery to muscle tissue.Expert opinion on drug delivery · 2014Review
- Developmental stage determines efficiency of gene transfer to muscle satellite cells by in utero delivery of adeno-associated virus vector serotype 2/9.Molecular therapy. Methods & clinical development · 2014Article
- Intramuscular injection of AAV8 in mice and macaques is associated with substantial hepatic targeting and transgene expression.PloS one · 2014Article
- Platelet gene therapy by lentiviral gene delivery to hematopoietic stem cells restores hemostasis and induces humoral immune tolerance in FIX(null) mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- AAV8 induces tolerance in murine muscle as a result of poor APC transduction, T cell exhaustion, and minimal MHCI upregulation on target cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Multiple recombinant adeno-associated viral vector serotypes display persistent in vivo gene expression in vector-transduced rat stifle joints.Human gene therapy methods · 2013Article
- The AAV vector toolkit: poised at the clinical crossroads.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Review
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 1 institution in 1 country.
Funding
Abstract
backgroundAdeno-associated viral vector (AAV)-mediated and muscle-directed gene therapy is a safe and non-invasive approach to treatment of hemophilia B and other genetic diseases. However, low efficiency of transduction, inhibitor formation and high prevalence of pre-existing immunity to the AAV capsid in humans remain as main challenges for AAV2-based vectors using this strategy. Vectors packaged with AAV7, 8 and 9 serotypes have improved gene transfer efficiencies and may provide potential alternatives to overcome these problems.
objectiveTo compare the long-term expression of canine factor IX (cFIX) levels and anti-cFIX antibody responses following intramuscular injection of vectors packaged with AAV1, 2, 5, 7, 8 and 9 capsid in immunocompetent hemophilia B mice.
resultsHighest expression was detected in mice injected with AAV2/8 vector (28% of normal), followed by AAV2/9 (15%) and AAV2/7 (10%). cFIX expression by AAV2/1 only ranged from 0 to 5% of normal levels. High incidences of anti-cFIX inhibitor (IgG) were detected in mice injected with AAV2 and 2/5 vectors, followed by AAV2/1. None of the mice treated with AAV2/7, 2/8 and 2/9 developed inhibitors or capsid T cells.
conclusionsAAV7, 8 and 9 are more efficient and safer vectors for muscle-directed gene therapy with high levels of transgene expression and absence of inhibitor formation. The absence of antibody response to transgene by AAV7, 8 and 9 is independent of vector dose but may be due to the fact that these three serotypes are associated with high level distribution to, and transduction of, hepatocytes following i.m. injection.
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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.