ArticleGene therapy2007
Transgene expression levels and kinetics determine risk of humoral immune response modeled in factor IX knockout and missense mutant mice.
Article in Gene therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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
24 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Gene Therapy Approaches for the Treatment of Hemophilia B.International journal of molecular sciences · 2023Review
- Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice.Blood advances · 2022Article
- Timely and large dose of clotting factor IX provides better joint wound healing after hemarthrosis in hemophilia B mice.International journal of hematology · 2019Article
- Toward Personalized Gene Therapy: Characterizing the Host Genetic Control of Lentiviral-Vector-Mediated Hepatic Gene Delivery.Molecular therapy. Methods & clinical development · 2017Article
- Effects of transgene expression level per cell in mice livers on induction of transgene-specific immune responses after hydrodynamic gene transfer.Gene therapy · 2016Article
- 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
- Animal models of hemophilia and related bleeding disorders.Seminars in hematology · 2013Review
- Animal models of hemophilia.Progress in molecular biology and translational science · 2012Review
- Inhibition and promotion of tumor growth with adeno-associated virus carcinoembryonic antigen vaccine and Toll-like receptor agonists.Cancer gene therapy · 2011Article
- Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver.Gene therapy · 2011Article
- Proteasome inhibitors enhance gene delivery by AAV virus vectors expressing large genomes in hemophilia mouse and dog models: a strategy for broad clinical application.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- AAV's anatomy: roadmap for optimizing vectors for translational success.Current gene therapy · 2010Article
- Regulatory T cells and immune tolerance to coagulation factor IX in the context of intramuscular AAV1 gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Article
- Naturally occurring singleton residues in AAV capsid impact vector performance and illustrate structural constraints.Gene therapy · 2009Article
- A new genetic vaccine platform based on an adeno-associated virus isolated from a rhesus macaque.Journal of virology · 2009Article
- Evading the immune response upon in vivo gene therapy with viral vectors.Current opinion in molecular therapeutics · 2009Review
- Impact of the underlying mutation and the route of vector administration on immune responses to factor IX in gene therapy for hemophilia B.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Induction of immune tolerance to FIX following muscular AAV gene transfer is AAV-dose/FIX-level dependent.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Immune responses leading to antibody-mediated elimination of the transgenic protein are a concern in gene replacement for congenital protein deficiencies, for which hemophilia is an important model. Although most hemophilia B patients have circulating non-functional but immunologically crossreactive factor IX (FIX) protein (CRM+ phenotype), inciting factors for FIX neutralizing antibody (inhibitor) development have been studied in crossreactive material-negative (CRM-) animal models. For this study, determinants of FIX inhibitor development were compared in hemophilia B mice, in which circulating FIX protein is absent (CRM- factor IX knockout (FIXKO) model) or present (CRM+ missense R333Q-hFIX model) modeling multiple potential therapies. The investigations compare for the first time different serotypes of adeno-associated virus (AAV) vectors (AAV2 and AAV1), each at multiple doses, in the setting of two different FIX mutations. The comparisons demonstrate in the FIXKO background (CRM- phenotype) that neither vector serotype nor vector particle number independently determine the inhibitor trigger, which is influenced primarily by the level and kinetics of transgene expression. In the CRM+ missense background, inhibitor development was never stimulated by AAV gene therapy or protein therapy, despite the persistence of lymphocytes capable of responding to FIX with non-inhibitory antibodies. This genotype/phenotype is strongly protective against antibody formation in response to FIX therapy.
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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.