Practical Applications

In 2011 we designed proteins that bind to conserved surfaces on influenza hemagglutinin from the 1918 H1N1 pandemic flu virus [14]. These durable antivirals protect rodents from exposure to lethal amounts of the virus [1]. Our researchers have also shown that these same flu binders can be used as diagnostic reagents in low-cost diagnostic test strips, providing improved performance as an influenza assay compared to a traditional antibody-based capture system [2]. These sensitive reagents can reliably detect less than 100 influenza virus particles on a single nasal swab. In 2020 we used this same platform technology to create potent antivirals for the pandemic coronavirus and adapted them into modular and sensitive biosensors [18, 19].

In 2013 we generated protein binders to the steroid drug digoxigenin, a drug often given to cardiac patients with atrial fibrillation or heart failure [11].  We went on to show that this protein could be used as a sensitive digoxigenin sensor [10] for point-of-care diagnostic applications, and also as a sensor in cells [12, 13]. In 2017 we used similar methods to design a high-affinity sensor for the potent opioid fentanyl [16]. Two years later we also developed a new protein-based sensor technology called LOCKR and showed that it can be used to direct cancer-killing T cell activity to precise cell populations, thereby avoiding unwanted drug activity. We also demonstrated that LOCKR technology can be reconfigured into a biosensor for detecting vaccine signatures in blood [19].

In 2011 a team of UW undergraduates working out of the IPD won the grand prize at the annual iGEM competition. They sought to develop a cure for celiac disease and used computational design to re-engineer a natural enzyme to break down gluten in the harsh acidic conditions of the stomach [6]. In 2015 our team published the most advanced version of the enzyme, dubbed Kuma030, which cleaves gluten molecules at sites that are known to cause an immune reaction in those with celiac disease. The enzyme was further developed by our spinout company PvP Biologics, which has been acquired by Takeda.

In 2014 our scientists were the first to demonstrate that computational design can be used to eliminate T-cell epitopes from proteins by altering the amino acid sequence without affecting structure or function [15]. This immune silencing approach enabled collaborators at the National Cancer Institute to improve an immunotoxin used to treat cancer. The new designed immunotoxins maintained good activity, stability, and antitumor activity. Their reduced immunogenicity will enable more effective cancer therapy as more treatment cycles can be given before an immune response is mounted to neutralize the therapy [4].