Christopher J. Walkey, Kathy J. Snow, Jote Bulcha, Aaron R. Cox, Alexa E. Martinez, M. Cecilia Ljungberg, Denise G. Lanza, Marco De Giorgi, Marcel A. Chuecos, Michele Alves-Bezerra, Carlos Flores Suarez, Sean M. Hartig, Susan G. Hilsenbeck, Chih-Wei Hsu, Ethan Saville, Yaned Gaitan, Jeff Duryea, Seth Hannigan, Mary E. Dickinson, Oleg Mirochnitchenko, Dan Wang, Cathleen M. Lutz, Jason D. Heaney, Guangping Gao, Steve A. Murray, William R. Lagor
{"title":"A Comprehensive Atlas of AAV Tropism in the Mouse","authors":"Christopher J. Walkey, Kathy J. Snow, Jote Bulcha, Aaron R. Cox, Alexa E. Martinez, M. Cecilia Ljungberg, Denise G. Lanza, Marco De Giorgi, Marcel A. Chuecos, Michele Alves-Bezerra, Carlos Flores Suarez, Sean M. Hartig, Susan G. Hilsenbeck, Chih-Wei Hsu, Ethan Saville, Yaned Gaitan, Jeff Duryea, Seth Hannigan, Mary E. Dickinson, Oleg Mirochnitchenko, Dan Wang, Cathleen M. Lutz, Jason D. Heaney, Guangping Gao, Steve A. Murray, William R. Lagor","doi":"10.1101/2024.09.10.612279","DOIUrl":null,"url":null,"abstract":"Gene therapy with Adeno-Associated Viral (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence. Cre-driven activation of tdTomato fluorescence offered superior sensitivity for transduced cells. All serotypes except AAV3B and AAV4 had high liver tropism. Fluorescence activation revealed transduction of unexpected tissues, including adrenals, testes and ovaries. Rare transduced cells within tissues were also readily visualized. Biodistribution of AAV genomes correlated with fluorescence, except in immune tissues. AAV4 was found to have a pan-endothelial tropism while also targeting pancreatic beta cells. This public resource enables selection of the best AAV serotypes for basic science and preclinical applications in mice.","PeriodicalId":501108,"journal":{"name":"bioRxiv - Molecular Biology","volume":"2 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Molecular Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.09.10.612279","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Gene therapy with Adeno-Associated Viral (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence. Cre-driven activation of tdTomato fluorescence offered superior sensitivity for transduced cells. All serotypes except AAV3B and AAV4 had high liver tropism. Fluorescence activation revealed transduction of unexpected tissues, including adrenals, testes and ovaries. Rare transduced cells within tissues were also readily visualized. Biodistribution of AAV genomes correlated with fluorescence, except in immune tissues. AAV4 was found to have a pan-endothelial tropism while also targeting pancreatic beta cells. This public resource enables selection of the best AAV serotypes for basic science and preclinical applications in mice.
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