A comprehensive atlas of AAV tropism in the mouse.
Summary
Systemic delivery of 10 AAV serotypes in mice revealed broad organ and cell tropism, including unexpected transduction of adrenals, testes, and ovaries. AAV4 exhibited pan-endothelial tropism and targeted pancreatic beta cells, and Cre-driven tdTomato activation provided superior sensitivity, creating a public atlas to guide serotype selection.
Key Findings
- Cre-driven tdTomato fluorescence provided superior sensitivity for detecting transduced cells compared with ZsGreen.
- All serotypes except AAV3B and AAV4 showed high liver tropism after systemic delivery.
- Unexpected endocrine and reproductive tissues (adrenals, testes, ovaries) displayed transduction.
- Biodistribution of AAV genomes correlated with fluorescence readouts except in immune tissues.
- AAV4 demonstrated pan-endothelial tropism and targeted pancreatic beta cells.
Clinical Implications
For endocrine gene therapy, these data support choosing specific serotypes (e.g., AAV4 for endothelial/beta-cell targeting) and anticipating off-target transduction (adrenals, gonads). It informs dosing, biodistribution, and safety planning in preclinical models.
Why It Matters
This resource enables rational vector selection for preclinical gene therapy, including endocrine targets such as pancreatic beta cells and adrenals. It uncovers novel AAV4 behavior (pan-endothelial and beta-cell tropism) with translational implications.
Limitations
- Mouse-only preclinical data; human translational tropism may differ.
- Quantitative dosing-to-transduction relationships and immune tissue discrepancies require further study.
Future Directions
Validate tropism in disease models and large animals; engineer capsids leveraging AAV4 endothelial/beta-cell properties; integrate single-cell and spatial omics to refine cell-type targeting maps.
Study Information
- Study Type
- Case series
- Research Domain
- Treatment
- Evidence Level
- V - Preclinical in vivo experimental mapping of vector tropism in mice.
- Study Design
- OTHER