Abstract

Using Organs-on-Chips for Screening Therapeutics for Pandemic Respiratory Infections

Jeffrey Borenstein, Co Program Leader, DRAPER

One of the most powerful applications of organs-on-chips is as a platform for generating human-relevant data in screening therapeutic candidates across various disease models.  Here we present recent therapeutic screening results obtained using the high throughput human primary tissue culture platform PREDICT96-ALI (Air Liquid Interface) across pandemic respiratory infections including Influenza A Virus (IAV) and the coronaviruses hCoV-NL63, hCoV-OC43 and SARS-CoV-2.  These platforms, seeded with human primary tracheobronchial epithelial cells obtained from commercial sources as well as directly from bronchoscopies performed on living donors, enable rapid screening across a range of conditions including infection levels, cell source, candidate compound and therapeutic dose.  In the case of SARS-CoV-2, this represents a first demonstration of successful therapeutic screening in a high containment BSL-3 environment.  Results from the airway platform correlate closely with clinical data, demonstrating a compelling opportunity for an organ-on-chip model to serve a critical role in evaluating potential candidates capable of efficaciously treating severe respiratory infections.