ArticleHuman gene therapy2011
Safety of liver gene transfer following peripheral intravascular delivery of adeno-associated virus (AAV)-5 and AAV-6 in a large animal model.
Article in Human gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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.
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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
14 citing papers in PubMed, 24 citations in OpenAlex.
- Trial
- Lack of germline transmission in male mice following a single intravenous administration of AAV5-hFVIII-SQ gene therapy.Gene therapy · 2023Article
- First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection.Molecular therapy. Methods & clinical development · 2020Article
- Mouse γ-Synuclein Promoter-Mediated Gene Expression and Editing in Mammalian Retinal Ganglion Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Non-clinical Safety and Efficacy of an AAV2/8 Vector Administered Intravenously for Treatment of Mucopolysaccharidosis Type VI.Molecular therapy. Methods & clinical development · 2017Article
- Optimization of adeno-associated virus vector-mediated gene transfer to the respiratory tract.Gene therapy · 2017Article
- Article
- Contemporary Animal Models For Human Gene Therapy Applications.Current gene therapy · 2015Review
- Biodistribution of AAV8 vectors expressing human low-density lipoprotein receptor in a mouse model of homozygous familial hypercholesterolemia.Human gene therapy. Clinical development · 2013Article
- Extracorporeal delivery of rAAV with metabolic exchange and oxygenation.Scientific reports · 2013Article
- Article
- Muscle Gene Therapy for Hemophilia.Journal of genetic syndromes & gene therapy · 2012Article
- Obstacles and future of gene therapy for hemophilia.Expert opinion on orphan drugsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Intravascular delivery of adeno-associated virus (AAV) vector is commonly used for liver-directed gene therapy. In humans, the high prevalence of neutralizing antibodies to AAV-2 capsid and the wide cross-reactivity with other serotypes hamper vector transduction efficacy. Moreover, the safety of gene-based approaches depends on vector biodistribution, vector dose, and route of administration. Here we sought to characterize the safety of AAV-5 and AAV-6 for liver-mediated human factor IX (hFIX) expression in rabbits at doses of 1 × 10(12) or 1 × 10(13) viral genomes/kg. Circulating therapeutic levels of FIX were observed in both cohorts of AAV-6-hFIX, whereas for AAV-5-hFIX only the high dose was effective. Long-lasting inhibitory antibodies to hFIX were detected in three of the 10 AAV-6-injected animals but were absent in the AAV-5 group. Overall, vector shedding in the semen was transient and vector dose-dependent. However, the kinetics of clearance were remarkably faster for AAV-5 (3-5 weeks) compared with AAV-6 (10-13 weeks). AAV-6 vector sequences outside the liver were minimal at 20-30 weeks post-injection. In contrast, AAV-5 exhibited relatively high amounts of vector DNA in tissues other than the liver. Together these data are useful to further define the safety and potential for clinical translation of these AAV vectors.
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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.