A comprehensive atlas of AAV tropism in the mouse

Christopher J Walkey¹, Kathy J Snow², Jote Bulcha³, Aaron R Cox⁴, Alexa E Martinez¹, M Cecilia Ljungberg⁵, Denise G Lanza⁶, Marco De Giorgi¹, Marcel A Chuecos¹, Michele Alves-Bezerra¹, Carlos Flores Suarez¹, Sean M Hartig⁷, Susan G Hilsenbeck⁸, Chih-Wei Hsu¹, Ethan Saville², Yaned Gaitan², Jeff Duryea Jr², Seth Hannigan², Mary E Dickinson¹, Oleg Mirochnitchenko⁹, Dan Wang¹⁰, Cathleen M Lutz², Jason D Heaney⁶, Guangping Gao³, Stephen A Murray², William R Lagor¹¹

Affiliations

¹ Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA.
² The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609 USA.
³ Horae Gene Therapy Center and Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA; Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA 01605, USA.
⁴ Section of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
⁶ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁷ Section of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
⁸ Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁹ Office of Research Infrastructure Programs, Division of Program Coordination, Planning, and Strategic Initiatives, Office of the Director, National Institutes of Health, Bethesda, MD USA.
¹⁰ Horae Gene Therapy Center and Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
¹¹ Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: william.lagor@bcm.edu.

PMID: 39863928
PMCID: PMC11897767 (available on 2026-03-05)
DOI: 10.1016/j.ymthe.2025.01.041

A comprehensive atlas of AAV tropism in the mouse

Christopher J Walkey et al. Mol Ther. 2025.

. 2025 Mar 5;33(3):1282-1299.

doi: 10.1016/j.ymthe.2025.01.041. Epub 2025 Jan 25.

Authors

Affiliations

¹ Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA.
² The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609 USA.
³ Horae Gene Therapy Center and Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA; Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA 01605, USA.
⁴ Section of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
⁶ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁷ Section of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
⁸ Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁹ Office of Research Infrastructure Programs, Division of Program Coordination, Planning, and Strategic Initiatives, Office of the Director, National Institutes of Health, Bethesda, MD USA.
¹⁰ Horae Gene Therapy Center and Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
¹¹ Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: william.lagor@bcm.edu.

PMID: 39863928
PMCID: PMC11897767 (available on 2026-03-05)
DOI: 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.

Keywords: AAV; AAV tropism; adeno-associated virus; biodistribution; fluorescent reporter; gene therapy; mouse models; serotypes; transduction.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

A Comprehensive Atlas of AAV Tropism in the Mouse.
Walkey CJ, Snow KJ, Bulcha J, Cox AR, Martinez AE, Ljungberg MC, Lanza DG, Giorgi M, Chuecos MA, Alves-Bezerra M, Suarez CF, Hartig SM, Hilsenbeck SG, Hsu CW, Saville E, Gaitan Y, Duryea J, Hannigan S, Dickinson ME, Mirochnitchenko O, Wang D, Lutz CM, Heaney JD, Gao G, Murray SA, Lagor WR. Walkey CJ, et al. bioRxiv [Preprint]. 2024 Sep 10:2024.09.10.612279. doi: 10.1101/2024.09.10.612279. bioRxiv. 2024. Update in: Mol Ther. 2025 Mar 05;33(3):1282-1299. doi: 10.1016/j.ymthe.2025.01.041. PMID: 39314496 Free PMC article. Updated. Preprint.

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A comprehensive atlas of AAV tropism in the mouse

Affiliations

A comprehensive atlas of AAV tropism in the mouse

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources