A comprehensive atlas of AAV tropism in the mouse.
Document Type
Article
Publication Date
3-5-2025
Original Citation
Walkey C,
Snow KJ,
Bulcha J,
Cox A,
Martinez A,
Ljungberg M,
Lanza D,
De Giorgi M,
Chuecos M,
Alves-Bezerra M,
Suarez C,
Hartig S,
Hilsenbeck S,
Hsu C,
Saville E,
Gaitan Y,
Duryea J,
Hannigan S,
Dickinson M,
Mirochnitchenko O,
Wang D,
Lutz C,
Heaney J,
Gao G,
Murray S,
Lagor W.
A comprehensive atlas of AAV tropism in the mouse. Mol Ther. 2025;33(3):1282-99.
Keywords
JMG, SS1, Animals, Dependovirus, Mice, Viral Tropism, Genetic Vectors, Female, Male, Transduction, Genetic, Transgenes, Humans, Genetic Therapy, Liver, Serogroup, Tissue Distribution
JAX Source
Mol Ther. 2025;33(3):1282-99.
ISSN
1525-0024
PMID
39863928
DOI
https://doi.org/10.1016/j.ymthe.2025.01.041
Abstract
Gene therapy with adeno-associated virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of 10 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.