New comprehensive atlas aims to optimise gene therapy delivery
Researchers have created a detailed map of adeno associated virus distribution in mice to improve targeting efficiency and reduce off-target effects in gene therapy applications.
A multi-institutional collaboration has produced what may become an essential resource for gene therapy researchers: a comprehensive atlas documenting how different adeno-associated viruses (AAVs) distribute genetic material across various tissues in mice. The study, published in the journal Molecular Therapy on 5 March 2025, provides critical information to help scientists select the most appropriate viral vectors for their specific research targets.
Expanding the knowledge base
The research team, led by scientists from Baylor College of Medicine, the Jackson Laboratory, and the University of Massachusetts Medical School, analysed the tissue distribution patterns of 10 distinct AAV vector types across 22 different tissues in both male and female mice.
“Over the last three decades, adeno-associated viruses (AAVs) have emerged as the leading gene delivery system in mice and people, due to their efficiency and favourable safety profile,” said first author Dr Christopher J. Walkey, assistant professor in integrative physiology at Baylor.
What sets this study apart from previous research is its comprehensive scope and methodological approach. The team employed fluorescent imaging techniques to examine organ sections, allowing them to assess gene delivery efficiency down to individual cells. “We analyzed more AAVs and tissues than those that have been studied before – 10 distinct types of AAVs in 22 different tissues, both in males and females,” explained corresponding author Dr William Lagor, Kyle and Josephine Morrow Endowed Professor of integrative physiology at Baylor.
Novel discoveries with therapeutic potential
The expanded approach led to several significant discoveries, including new insights about AAV4, a viral vector that had not been extensively studied previously. The researchers found that AAV4 efficiently delivers genetic material to endothelial cells in blood vessels and beta cells in the pancreas while largely avoiding the liver – a common target for most other AAV varieties.
“These findings with AAV4 open the door for gene therapies directed at vascular tissues, which have not yet been successful,” Walkey said. “And the affinity of AAV4 toward beta cells in the pancreas, the producers of insulin, makes it a potential candidate for gene therapy for diabetes.”
A publicly available resource
TThe atlas has been made publicly available online, with the researchers hoping it will accelerate both basic research and clinical applications.
“We hope that this resource will help researchers engineer better gene therapy vectors for human conditions,” Lagor said. “This will be useful across many disciplines which rely on AAV vectors for gene delivery in basic research. It will also make preclinical gene therapy studies in mice more efficient and reproducible, given that a lot of the homework on the best AAV for a given cell type has already been done.”
Collaborative science in action
The study exemplifies the power of scientific collaboration, bringing together experts from multiple disciplines and institutions. The work was supported by the NIH’s Somatic Cell Genome Editing Consortium, with AAV design and production handled by researchers at UMass Medical School, fluorescent imaging experiments conducted by a team at Jackson Labs, and tissue distribution analysis performed by scientists at Baylor College of Medicine. “This project would not have been possible without such an outstanding team of collaborators,” Dr Lagor said. “It is a great example of the value of teamwork and replication in science. We were able to readily confirm the results of our colleagues at Jackson Labs, which really improved our confidence in the findings, and vice versa. We appreciate the critical role NIH played in supporting this important project.”
Reference:
Walkey, C. J., et al. (2025). A comprehensive atlas of AAV tropism in the mouse. Molecular Therapy. March 5, 2025.
doi: https://doi.org/10.1016/j.ymthe.2025.01.041
Experiment:
AAV Tropism project is available online here: https://shorturl.at/Lo9kI
