A Faster, Human-Based Approach To AAV Optimization With The Emulate Liver-Chip

In vivo gene therapy shows great potential for treating both inherited and acquired genetic diseases that affect the liver. Developing an effective transgene is only part of the solution; it is equally important to create an efficient and safe delivery vehicle for the transgene to reach the target cells.

Developing these delivery vehicles presents significant challenges. Traditional research models have limitations, 2D cell culture models lack the complexity for physiological relevance, and animal studies are tightly regulated, expensive, and time-consuming. These hurdles have slowed the advancement of gene therapy, delaying the delivery of safe and effective treatments to patients in need.

Rather than waiting months for results from animal studies that may not translate to humans, researchers can obtain physiologically relevant data in weeks using the Emulate Liver-Chip to evaluate gene therapy vectors. Through the adeno-associated virus (AAV) transduction application for the Liver-Chip, researchers can test the delivery efficiency and toxicity of AAV vectors in a human-relevant in vitro liver sinusoid model. This application is validated for predicting drug toxicity, enabling the rapid iteration of AAV designs to improve the delivery of gene therapies and accelerate their development.

Watch to learn how the Liver-Chip has been utilized to measure time- and concentration-dependent AAV transduction efficiency, compare the transduction efficiency of various AAVs, evaluate the toxicity of AAV-based gene therapy vectors, and study the transport of AAVs from the vasculature to target epithelial tissue in a proof-of-concept study.