Author:
Walkey Christopher J.,Snow Kathy J.,Bulcha Jote,Cox Aaron R.,Martinez Alexa E.,Ljungberg M. Cecilia,Lanza Denise G.,Giorgi Marco De,Chuecos Marcel A.,Alves-Bezerra Michele,Suarez Carlos Flores,Hartig Sean M.,Hilsenbeck Susan G.,Hsu Chih-Wei,Saville Ethan,Gaitan Yaned,Duryea Jeff,Hannigan Seth,Dickinson Mary E.,Mirochnitchenko Oleg,Wang Dan,Lutz Cathleen M.,Heaney Jason D.,Gao Guangping,Murray Stephen A.,Lagor William R.
Abstract
SummaryGene 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.
Publisher
Cold Spring Harbor Laboratory