ArticleNature biotechnology2021
A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells.
Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 241 papers, 1 of them a synthesis that pooled it.
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Who cites it
241 citing papers in PubMed, 1 synthesis or guideline pooled it, 436 citations in OpenAlex.
- Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice.Blood advances · 2024Guideline
- Defining the safety and efficacy of liver-directed AAV gene therapy using a human liver tissue-equivalent platform.Molecular therapy. Advances · 2026Article
- Long-read target enrichment sequencing for rAAV integration site analysis in engineered clones with targeted viral insertion.Molecular therapy. Nucleic acids · 2026Article
- Article
- Development of an Agent-Based Model to Investigate Durability of Factor IX Activity in Hemophilia B Patients Treated With Etranacogene Dezaparvovec.CPT: pharmacometrics & systems pharmacology · 2026Article
- Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?Toxicologic pathology · 2026Review
- Topical application of Cas9 ribonucleoproteins inhibits corneal neovascularization in a mouse model of alkali burn injury.Gene therapy · 2026Article
- Comparative Analysis of rAAV Production from Plasmid-Encoded Versus Chromosomally Integrated rAAV Transgene in HEK293 Cells.International journal of molecular sciences · 2026Article
- intmap: fast and flexible mapping of mobile DNA integration for basic and translational research.Bioinformatics (Oxford, England) · 2026Article
- Long-term comparative analysis of AAV9-mediated gene replacement therapies for spinal muscular atrophy in mice.Nature communications · 2026Article
- AviTag-seq unifies nucleotide-resolution maps of CRISPR off-targets and AAV vector integrations.Communications biology · 2026Article
- Messenger RNA delivery into Sertoli cells restores fertility to congenitally infertile male mice.Stem cell reports · 2026Article
- RAAVioli: A comprehensive approach to characterizing AAV vector integrations and rearrangements.Molecular therapy. Advances · 2026Article
- Article
- Advancements in RNA-based therapies from bench to bedside.npj drug discovery · 2026Review
- Biomaterial-assisted neuralization strategies for tissue engineering applications.Materials today. Bio · 2026Review
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- Balancing Promise and Peril: Hemophilia Gene Therapy Insights.IUBMB life · 2026Review
- Malignancy and gene therapy in hemophilia.Research and practice in thrombosis and haemostasis · 2026Article
- Current Status of Clinical Gene Therapy for Hemophilia and Globin Disorders.Journal of blood medicine · 2026Review
181 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Nine dogs with hemophilia A were treated with adeno-associated viral (AAV) gene therapy and followed for up to 10 years. Administration of AAV8 or AAV9 vectors expressing canine factor VIII (AAV-cFVIII) corrected the FVIII deficiency to 1.9-11.3% of normal FVIII levels. In two of nine dogs, levels of FVIII activity increased gradually starting about 4 years after treatment. None of the dogs showed evidence of tumors or altered liver function. Analysis of integration sites in liver samples from six treated dogs identified 1,741 unique AAV integration events in genomic DNA and expanded cell clones in five dogs, with 44% of the integrations near genes involved in cell growth. All recovered integrated vectors were partially deleted and/or rearranged. Our data suggest that the increase in FVIII protein expression in two dogs may have been due to clonal expansion of cells harboring integrated vectors. These results support the clinical development of liver-directed AAV gene therapy for hemophilia A, while emphasizing the importance of long-term monitoring for potential genotoxicity.
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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.