ArticleJournal of virology2013
C-reactive protein (CRP) is essential for efficient systemic transduction of recombinant adeno-associated virus vector 1 (rAAV-1) and rAAV-6 in mice.
Article in Journal of virology, 2013. 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Viral-mediated gene therapy in pediatric neurological disorders.World journal of pediatrics : WJP · 2024Review
- Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.Journal of clinical medicine · 2023Review
- Review
- Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.Molecular therapy. Methods & clinical development · 2022Review
- Testing preexisting antibodies prior to AAV gene transfer therapy: rationale, lessons and future considerations.Molecular therapy. Methods & clinical development · 2022Review
- Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022Review
- Overcoming the Challenges Imposed by Humoral Immunity to AAV Vectors to Achieve Safe and Efficient Gene Transfer in Seropositive Patients.Frontiers in immunology · 2022Review
- The intersection of vector biology, gene therapy, and hemophilia.Research and practice in thrombosis and haemostasis · 2021Review
- Emerging Immunogenicity and Genotoxicity Considerations of Adeno-Associated Virus Vector Gene Therapy for Hemophilia.Journal of clinical medicine · 2021Review
- Adeno-Associated Viruses (AAV) and Host Immunity - A Race Between the Hare and the Hedgehog.Frontiers in immunology · 2021Review
- Bound Protein- and Peptide-Based Strategies for Adeno-Associated Virus Vector-Mediated Gene Therapy: Where Do We Stand Now?Human gene therapy · 2020Article
- Adeno-associated virus-binding antibodies detected in cats living in the Northeastern United States lack neutralizing activity.Scientific reports · 2020Article
- Article
- Engineering adeno-associated virus vectors for gene therapy.Nature reviews. Genetics · 2020Review
- AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Human Immune Responses to Adeno-Associated Virus (AAV) Vectors.Frontiers in immunology · 2020Review
- AAV-8 and AAV-9 Vectors Cooperate with Serum Proteins Differently Than AAV-1 and AAV-6.Molecular therapy. Methods & clinical development · 2018Article
- AAV8 virions hijack serum proteins to increase hepatocyte binding for transduction enhancement.Virology · 2018Article
- Direct interaction of human serum proteins with AAV virions to enhance AAV transduction: immediate impact on clinical applications.Gene therapy · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical relevance of gene therapy using the recombinant adeno-associated virus (rAAV) vectors often requires widespread distribution of the vector, and in this case, systemic delivery is the optimal route of administration. Humoral blood factors, such as antibodies or complement, are the first barriers met by the vectors administered systemically. We have found that other blood proteins, galectin 3 binding protein (G3BP) and C-reactive protein (CRP), can interact with different AAV serotypes in a species-specific manner. While interactions of rAAV vectors with G3BP, antibodies, or complement lead to a decrease in vector efficacy, systemic transduction of the CRP-deficient mouse and its respective control clearly established that binding to mouse CRP (mCRP) boosts rAAV vector 1 (rAAV-1) and rAAV-6 transduction efficiency in skeletal muscles over 10 times. Notably, the high efficacy of rAAV-6 in CRP-deficient mice can be restored by reconstitution of the CRP-deficient mouse with mCRP. Human CRP (hCRP) does not interact with either rAAV-1 or rAAV-6, and, consequently, the high efficiency of mCRP-mediated muscle transduction by these serotypes in mice cannot be translated to humans. No interaction of mCRP or hCRP was observed with rAAV-8 and rAAV-9. We show, for the first time, that serum components can significantly enhance rAAV-mediated tissue transduction in a serotype- and species-specific manner. Bioprocessing in body fluids should be considered when transfer of a preclinical proof of concept for AAV-based gene therapy to humans is planned.
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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.