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PubMed:25404742 JSONTXT 18 Projects

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Id Subject Object Predicate Lexical cue
T1 0-91 Sentence denotes Functional analysis of the putative integrin recognition motif on adeno-associated virus 9.
T2 92-183 Sentence denotes Adeno-associated viruses (AAVs) display a highly conserved NGR motif on the capsid surface.
T3 184-342 Sentence denotes Earlier studies have established this tripeptide motif as being essential for integrin-mediated uptake of recombinant AAV serotype 2 (AAV2) in cultured cells.
T4 343-509 Sentence denotes However, functional attributes of this putative integrin recognition motif in other recombinant AAV serotypes displaying systemic transduction in vivo remain unknown.
T5 510-628 Sentence denotes In this study, we dissect the biology of an integrin domain capsid mutant derived from the human isolate AAV9 in mice.
T6 629-695 Sentence denotes The AAV9/NGA mutant shows decreased systemic transduction in mice.
T7 696-845 Sentence denotes This defective phenotype was accompanied by rapid clearance of mutant virions from the blood circulation and nonspecific sequestration by the spleen.
T8 846-978 Sentence denotes Transient vascular hyperpermeability, induced by histamine coinjection, exacerbated AAV9/NGA uptake by the spleen but not the liver.
T9 979-1115 Sentence denotes However, such treatment did not affect AAV9 virions, suggesting a potential entry/post-entry defect for the mutant in different tissues.
T10 1116-1259 Sentence denotes Further characterization revealed modestly decreased cell surface binding but a more pronounced defect in the cellular entry of mutant virions.
T11 1260-1453 Sentence denotes These findings were corroborated by the observation that blocking multiple integrins adversely affected recombinant AAV9 transduction in different cell types, albeit with variable efficiencies.
T12 1454-1781 Sentence denotes 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.