Language

English

Publication Date

3-5-2025

Journal

Molecular Therapy

DOI

10.1016/j.ymthe.2025.01.041

PMID

39863928

PMCID

PMC11897767

PubMedCentral® Posted Date

1-25-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Dependovirus, Animals, Mice, Genetic Vectors, Female, Viral Tropism, Male, Transduction, Genetic, Humans, Tissue Distribution, Transgenes, Serogroup, Genetic Therapy

Published Open-Access

yes

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