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• W4387660767 abstract "AAV7 is a clade D adeno-associated virus (AAV) whose potential as a gene therapy vector has not been fully evaluated. We show here that high-titer AAV7 vectors can be produced in HEK293 cells and used to transduce cultured cells in an AAV receptor (AAVR)-dependent manner. In contrast with AAV9, AAV7 did not significantly interact with glycans when assayed on a panel of three hundred biologically relevant species. The structure of the AAV7 capsid was obtained by single particle cryo-electron microscopy at 2.7 Å, showing the expected AAV scaffold as well as unique features in variable surface loops. The biodistribution profiles of AAV7 and AAV9 vectors were compared in mice following intravenous administration and quantification of vector genomes and mRNA in tissues, as well as cryofluorescence tomography (CFT) and immunofluorescence (IF). AAV7 displayed a strong cardiac tropism and did not efficiently cross the blood-brain barrier. Surprisingly, strong transgene expression was observed throughout the head as shown by CFT, including regions of the cranial sinuses, teeth, and mandible for both AAV7 and AAV9, an attribute that has not been previously evaluated via traditional biodistribution methods. IMPORTANCE The use of adeno-associated viruses (AAVs) as gene delivery vectors has vast potential for the treatment of many severe human diseases. Over one hundred naturally existing AAV capsid variants have been described and classified into phylogenetic clades based on their sequences. AAV8, AAV9, AAVrh.10, and other intensively studied capsids have been propelled into pre-clinical and clinical use, and more recently, marketed products; however, less-studied capsids may also have desirable properties (e.g., potency differences, tissue tropism, reduced immunogenicity, etc.) that have yet to be thoroughly described. These data will help build a broader structure-function knowledge base in the field, present capsid engineering opportunities, and enable the use of novel capsids with unique properties." @default.
• W4387660767 created "2023-10-17" @default.
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• W4387660767 date "2023-10-16" @default.
• W4387660767 modified "2023-10-17" @default.
• W4387660767 title "Characterization and biodistribution of under-employed gene therapy vector AAV7" @default.
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• W4387660767 doi "https://doi.org/10.1128/jvi.01163-23" @default.
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