ArticleHuman gene therapy2006
Efficient AAV1-AAV2 hybrid vector for gene therapy of hemophilia.
Article in Human gene therapy, 2006. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Trial
- A robust and flexible baculovirus-insect cell system for AAV vector production with improved yield, capsid ratios and potency.Molecular therapy. Methods & clinical development · 2024Article
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Single amino acid insertion allows functional transduction of murine hepatocytes with human liver tropic AAV capsids.Molecular therapy. Methods & clinical development · 2021Article
- Adeno-associated virus as a gene therapy vector: strategies to neutralize the neutralizing antibodies.Clinical and experimental medicine · 2019Review
- Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- E Pluribus Unum: 50 Years of Research, Millions of Viruses, and One Goal--Tailored Acceleration of AAV Evolution.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Review
- In vivo enrichment of genetically manipulated platelets corrects the murine hemophilic phenotype and induces immune tolerance even using a low multiplicity of infection.Journal of thrombosis and haemostasis : JTH · 2014Article
- An adeno-associated virus vector efficiently and specifically transduces mouse skeletal muscle.Molecular biotechnology · 2011Article
- Enhanced factor VIII heavy chain for gene therapy of hemophilia A.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Tailoring the AAV vector capsid for gene therapy.Gene therapy · 2009Review
- Article
- The role of the adeno-associated virus capsid in gene transfer.Methods in molecular biology (Clifton, N.J.) · 2008Review
- Existence of transient functional double-stranded DNA intermediates during recombinant AAV transduction.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) serotype 1 (AAV1) has been shown to be more effective than the well-studied AAV serotype 2 (AAV2) in muscle gene transfer. Replacement of amino acids 350 to 430 of AAV2 VP1 with the corresponding amino acids from VP1 of AAV1 resulted in a hybrid vector, termed AAV-221-IV, which behaved similarly to AAV1 in vitro and in vivo in muscle. Intramuscular injection of 1x10(11) vector particles per mouse of hybrid vector carrying a human FIX transgene in CD4 knockout mice resulted in an average level of human FIX in the plasma of 450 ng/ml, 4- to 10-fold higher than in mice injected with an AAV2 vector carrying the same transgene, and 80% of the transgene levels in animals treated with the same dose of AAV1. DNA analysis of injected muscle showed a 10-fold higher copy number after gene delivery by the hybrid vector compared with AAV2. A comparison of total DNA versus DNA from intact virus particles suggests a higher stability of hybrid virus particles. These results suggest that changes in the AAV capsid have an effect on virus-cell receptor interaction, and also influence trafficking and processing of the virus particle in the cell. This "hybrid vector" retains the heparin-binding sites of AAV2 and, therefore, can be purified by passage through a heparin-Sepharose column with the same efficiency as AAV2. When tested in vivo, either in CD4 knockout mice or in a hemophilic mouse model, the heparin-purified hybrid vector showed >10-fold higher activity than similarly purified AAV2. This demonstrates the utility of this hybrid vector in the performance of large-scale heparin column purification to generate a vector with a high expression profile for muscle-directed gene delivery. Initiation of clinical studies with this hybrid vector may be facilitated because it differs from AAV2 by only nine amino acids.
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What OpenQuestion holds
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.