Understanding how AAV vectors interact with human liver tissue is essential for improving both efficacy and safety. However, conventional in vitro models often fail to reproduce the complexity of the liver microenvironment, while animal studies do not always accurately predict clinical outcomes.
This collaborative study explores the use of Javelin Liver Tissue Chips as a physiologically relevant microphysiological system (MPS) for evaluating AAV vectors in a controlled human liver model. By integrating primary human hepatocytes with supporting liver cell populations in a perfused environment, the platform enables simultaneous assessment of vector transduction, cellular tropism, inflammatory responses and hepatotoxicity over extended culture periods.
Researchers compared clinically relevant AAV vectors, including AAV5, AAV8 and an engineered capsid, examining dose-dependent transduction, immune-related biomarkers and cell-type-specific targeting. The findings demonstrate that the Liver Tissue Chip captures biologically meaningful differences between vectors while providing valuable insight into liver-specific responses that may support preclinical vector characterization.
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Liver Tissue Chips for multidimensional AAV characterization