ArticleJournal of translational medicine2017
Evaluation of engineered AAV capsids for hepatic factor IX gene transfer in murine and canine models.
Article in Journal of translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 19 citations in OpenAlex.
- Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency.Cell death discovery · 2025Article
- Review
- Multiplexing AAV Serotype-Specific Neutralizing Antibodies in Preclinical Animal Models and Humans.Biomedicines · 2023Article
- Chimeric Mice Engrafted With Canine Hepatocytes Exhibits Similar AAV Transduction Efficiency to Hemophilia B Dog.Frontiers in pharmacology · 2022Article
- Engineering andMolecular therapy. Methods & clinical development · 2020Article
- Modifiers of Adeno-Associated Virus-Mediated Gene Expression in Implication for Serotype-Universal Neutralizing Antibody Assay.Human gene therapy · 2020Article
- Development of a Clinical Candidate AAV3 Vector for Gene Therapy of Hemophilia B.Human gene therapy · 2020Article
- Impact of Natural or Synthetic Singletons in the Capsid of Human Bocavirus 1 on Particle Infectivity and Immunoreactivity.Journal of virology · 2020Article
- Engineering adeno-associated virus vectors for gene therapy.Nature reviews. Genetics · 2020Review
- Superior human hepatocyte transduction with adeno-associated virus vector serotype 7.Gene therapy · 2019Article
- Liver induced transgene tolerance with AAV vectors.Cellular immunology · 2019Review
- Translation of MicroRNA-Based Huntingtin-Lowering Therapies from Preclinical Studies to the Clinic.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Review
- Emerging Issues in AAV-MediatedMolecular therapy. Methods & clinical development · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAdeno-associated virus (AAV) gene therapy vectors have shown the best outcomes in human clinical studies for the treatment of genetic diseases such as hemophilia. However, these pivotal investigations have also identified several challenges. For example, high vector doses are often used for hepatic gene transfer, and cytotoxic T lymphocyte responses against viral capsid may occur. Therefore, achieving therapy at reduced vector doses and other strategies to reduce capsid antigen presentation are desirable.
methodsWe tested several engineered AAV capsids for factor IX (FIX) expression for the treatment of hemophilia B by hepatic gene transfer. These capsids lack potential phosphorylation or ubiquitination sites, or had been generated through molecular evolution.
resultsAAV2 capsids lacking either a single lysine residue or 3 tyrosine residues directed substantially higher coagulation FIX expression in mice compared to wild-type sequence or other mutations. In hemophilia B dogs, however, expression from the tyrosine-mutant vector was merely comparable to historical data on AAV2. Evolved AAV2-LiC capsid was highly efficient in hemophilia B mice but lacked efficacy in a hemophilia B dog.
conclusionsSeveral alternative strategies for capsid modification improve the in vivo performance of AAV vectors in hepatic gene transfer for correction of hemophilia. However, capsid optimization solely in mouse liver may not predict efficacy in other species and thus is of limited translational utility.
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