ArticleThe Journal of biological chemistry2015
Functional analysis of the putative integrin recognition motif on adeno-associated virus 9.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- AAV-mediated co-expression of an immunogenic transgene plus PD-L1 enables sustained expression through immunological evasion.Scientific reports · 2024Article
- Molecular Engineering of Virus Tropism.International journal of molecular sciences · 2024Review
- Review
- Outer retinal transduction by AAV2-7m8 following intravitreal injection in a sheep model of CNGA3 achromatopsia.Gene therapy · 2022Article
- Molecular Signature of Astrocytes for Gene Delivery by the Synthetic Adeno-Associated Viral Vector rAAV9P1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Receptor Switching in Newly Evolved Adeno-associated Viruses.Journal of virology · 2021Article
- Adeno-associated virus (AAV)-based gene therapy for glioblastoma.Cancer cell international · 2021Review
- Structure comparison of the chimeric AAV2.7m8 vector with parental AAV2.Journal of structural biology · 2020Article
- Protease-Activatable Adeno-Associated Virus Vector for Gene Delivery to Damaged Heart Tissue.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- A Rationally Engineered Capsid Variant of AAV9 for Systemic CNS-Directed and Peripheral Tissue-Detargeted Gene Delivery in Neonates.Molecular therapy. Methods & clinical development · 2018Article
- Site Specific Modification of Adeno-Associated Virus Enables Both Fluorescent Imaging of Viral Particles and Characterization of the Capsid Interactome.Scientific reports · 2017Article
- In vivo tissue-tropism of adeno-associated viral vectors.Current opinion in virology · 2016Review
- Cryo-electron Microscopy Reconstruction and Stability Studies of the Wild Type and the R432A Variant of Adeno-associated Virus Type 2 Reveal that Capsid Structural Stability Is a Major Factor in Genome Packaging.Journal of virology · 2016Article
- Engineering AAV receptor footprints for gene therapy.Current opinion in virology · 2016Review
- Widespread Central Nervous System Gene Transfer and Silencing After Systemic Delivery of Novel AAV-AS Vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Structure of neurotropic adeno-associated virus AAVrh.8.Journal of structural biology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Adeno-associated viruses (AAVs) display a highly conserved NGR motif on the capsid surface. Earlier studies have established this tripeptide motif as being essential for integrin-mediated uptake of recombinant AAV serotype 2 (AAV2) in cultured cells. However, functional attributes of this putative integrin recognition motif in other recombinant AAV serotypes displaying systemic transduction in vivo remain unknown. In this study, we dissect the biology of an integrin domain capsid mutant derived from the human isolate AAV9 in mice. The AAV9/NGA mutant shows decreased systemic transduction in mice. This defective phenotype was accompanied by rapid clearance of mutant virions from the blood circulation and nonspecific sequestration by the spleen. Transient vascular hyperpermeability, induced by histamine coinjection, exacerbated AAV9/NGA uptake by the spleen but not the liver. However, such treatment did not affect AAV9 virions, suggesting a potential entry/post-entry defect for the mutant in different tissues. Further characterization revealed modestly decreased cell surface binding but a more pronounced defect in the cellular entry of mutant virions. These findings were corroborated by the observation that blocking multiple integrins adversely affected recombinant AAV9 transduction in different cell types, albeit with variable efficiencies. From a structural perspective, we observed that the integrin recognition motif is located in close proximity to the galactose binding footprint on AAV9 capsids and postulate that this feature could influence cell surface attachment, cellular uptake at the tissue level, and systemic clearance by the reticuloendothelial system.
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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.